Acute coronary syndrome (ACS), a term used to cover a group of clinical symptoms compatible with acute myocardial ischemia, represents a high-risk group of patients with coronary heart disease (CHD). To improve quality of care, international guidelines for the management of ACS have been established and are updated regularly. In the era of evidence based medicine, adherence to therapeutic guidelines is essential for optimal care of ACS patients. However, most data on ACS epidemiology, treatment and outcomes are derived from western population. There are limited data in Chinese population in terms of prevalence, presentation, response to treatment and clinical outcome. / Among 624 patients finished Short Form (SF)-36 questionnaires, health related quality of life (HRQoL) were compared between patients underwent PCI versus those treated conservatively across 3 age groups (<60, 60-79 and ≥80 years). PCI was performed in 73.6%,55.7% and 21.3% in patients aged <60,60-79 and older than 80 years, respectively (p<0.01). Elderly patients were more likely to be female (16.9 vs. 35.4 vs. 54.6%, p<0.01) and had more co-morbidities (p<0.01). Older patients were less likely to undergo angiography (84.8 vs. 65.2 vs. 24.8%, p<0.01). Baseline HRQoL decreased with advancing age (p<0.01). However, elderly patients who underwent PCI-experienced the most improvement in physical health than younger age groups. PCI was an independent predictor (OR, 1.79,95% CI: 1.10-2.92) of better physical health status at 6 months. In conclusion, elderly ACS patients who underwent PCI experienced the most improvement in physical health compared to younger patients. Our findings suggest that age per se should not deter against revascularization because of potential benefits in HRQOL. / In summary, this is the first registry which described patients' characteristics, treatment and management practices, and hospital outcomes over the whole spectrum of ACS in Hong Kong. The study identified gaps between guideline and clinical practice as well as the reasons of these gaps, and measured the impact of such gaps on the outcomes of patients with ACS. Compared with internationally reported data, Hong Kong patients are different in terms of age and risk factors distribution. Treatment gaps exist between international therapeutic guideline recommendations and clinical practice, especially among the high risk population, the elderly and female patients. Better understanding and narrowing these gaps between guideline and practice will lead to improvement in quality of care and clinical outcomes. Increase use ofrisk stratification models and health status assessments may improve decision making in the management of ACS. / Patients with ACS were divided into low- and high-predicted risk of mortality at 6 months using the GRACE risk score (≥142.5 was defined as high-risk). We evaluated the use of in-hospital angiography, revascularization, anti-platelet, angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), beta-blockers and statins therapy between high and low-risk patients. There were 259 patients in the high- and 742 in the low-risk groups. Paradoxically, high-risk compared to low-risk patients were less likely to underwent coronary angiography and/or revascularization during the index hospitalization (33% vs. 64% and 25% vs. 50%, both p<0.01). Hospital initiated pharmacotherapies are also lower in high-risk patients (24% vs. 55% for c1opidogrel, 49% vs. 58% for ACEI/ARBs, 54% vs. 69% for beta-blockers and 56% vs. 77% for statins; all p<0.01). After adjustment, high-risk patients remained less likely to undergo revascularization (adjusted odds ratio [OR], 0.47; 95% CI, 0.33-0.73, p<0.001) than low-risk patients. Advanced age, increased creatinine level and higher GRACE score were independent predictors for failure to administer evidence-based therapies. Thus, patients with ACS at high risk of mortality were paradoxically less likely to undergo revascularization or receive medications according to guidelines. Better adherence to evidence-based therapies in high-risk patients may improve clinical outcome and quality of health care. / The Hong Kong ACS registry was designed to investigate epidemiology, treatment and outcome of ACS patients under current medical care system, it was conducted in a university affiliated teaching hospital from February 2006 to December 2009. Clinical characteristics and treatment data were collected at baseline, 30 days and 6 months after onset in a standard defined case report form. SF-36 questionnaire was completed after admission and at 6 months. Outcomes were evaluated mortality and morbidity in clinical aspect and quality of life in aspect of health status. / The Main findings were as followed: Totally 1001 patients admitted with ACS were recruited. Among all patients enrolled, 31.7% were diagnosed with ST-segment elevation myocardial infarction, 42.7% with non-S'T-segrnent myocardial infarction and 21.6% with unstable angina. The median age was 72 (interquartile range 61-79) years; 77.2% were >60 years old, and 31.5% were women. / Women presented more often with NSTE-ACS than men (77.3% of women vs. 63.2% of men, p<0.001). Despite having greater cornorbidities including hypertension, diabetes, hypercholesterolemia, renal impairment and history of heart failure etc., women were observed to have higher GRACE (global registry of acute coronaryevents) score than men (128+/-32 vs. 118+/-37, p score than men (128+/-32 vs. 118+/-37, p<0.01). Women were less likely to be assigned invasive procedures (43.3% vs. 62.9%, p<0.001) as well as pharmacotherapies such as clopidogrel (41.1% vs. 58.8%, p<0.001), glycoprotein (GP) IIb/IIIa antagonists (5.3% vs. 11.6%, p=0.001) and statins (64.1% vs. 77.2%, p<0.01) et al. than men. For in-hospital mortality, the adjusted odds ratio for men compared to women was similar (odds ratio [OR]: 1.32, 95% CI: 0.62-2.83, p=0.47). The higher 6 month mortality and major cardiac events rate in women were not significant after adjusting for differences in clinical characteristics and percutaneous coronary intervention (PCI) (OR=1.02; 95% CI 0.62 to 1.68; p=0.95). In summary, there were differences in baseline characteristics and in the management of women and men admitted for ACS. Advanced age and high comorbidities prevalence could explain most of the difference between genders suggesting that decision making bias in clinical practice is anti-age but not anti-female. Overall, in-hospital and 6 months mortality was similar for women and men after adjustments. / Li, Rujie. / "December 2010." / Adviser: Cheuk-Man Yu. / Source: Dissertation Abstracts International, Volume: 73-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 145-166). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

A genética forense vem se desenvolvendo cada vez mais, com novas tecnologias e implementação de novos conjuntos de marcadores de DNA com maiores níveis de informatividade. Os marcadores genéticos são amplamente usados na identificação humana, pois permitem distinguir indivíduos com alta acurácia. Duas classes de marcadores muito utilizadas atualmente são os STRs (Short Tandem Repeats) e os SNPs (Single Nucleotide Polymorphisms). Os STRs são altamente informativos e, portanto, úteis para a prática forense. Kits mais novos como GlobalFiler (Thermo Fisher Scientific) e PowerPlex Fusion System (Promega) apresentam a análise de mais de 20 loci STRs de uma só vez. Já os SNPs, por possuírem sua informatividade mais reduzida (necessita de mais loci analisados), são menos utilizados, porém apresentam vantagem em amostras degradadas de DNA; assim, conjuntos de identificação como o 52-plex desenvolvido pelo consórcio SNPforID e o conjunto IISNPs, vêm sendo estudados em várias populações do mundo. Com o desenvolvimento de técnicas de sequenciamento de nova geração (NGS Next Generation Sequencing) para análise de DNA, a obtenção de perfis de DNA se tornou mais acurada. Algumas plataformas permitem gerar perfis de até 96 indivíduos simultaneamente. Este estudo tem por objetivo principal analisar 171 marcadores genéticos (Amelogenina, Y-INDEL, 30 STRSs e 139 SNPs) em 340 indivíduos miscigenados da região da cidade de Ribeirão Preto (SP) utilizando a plataforma de sequenciamento de nova geração MiSeq Personal Sequencer (Illumina Inc.), bem como calcular as frequências alélicas e genotípicas, verificar a aderência ao equilíbrio de HardyWeinberg e estimar parâmetros forenses para os diferentes conjuntos de marcadores. Análises de ancestralidade foram realizadas para os conjuntos de SNPs. Para o preparo das bibliotecas de amostras a serem sequenciadas, foi utilizado o kit HaloPlex (Agilent Technologies, Inc), onde foram incluídos os marcadores dos kits GlobalFiler e PowerPlex Fusion System, e os SNPs existentes no conjunto do consórcio SNPforID (52-plex) e IISNPs (92 SNPs). De todos os marcadores incluídos no ensaio, apenas um SNP (rs763869) presente no conjunto SNPforID não pôde ser analisado devido a questões técnicas. Dos 139 SNPs analisados apenas seis apresentaram desvios significativos em relação ao equilíbrio de Hardy-Weinberg,número este esperado devido ao acaso. Os conjuntos de SNPs apresentam elevada informatividade com Probabilidade de Match de 6,48 x 10-21 (52-plex) a 4,91 x 10-38 (IISNP), e Poder de Exclusão de 0,9997 (52-plex) e 0,99999997 (IISNP). De modo geral, as inferências de ancestralidade obtida utilizando estes conjuntos, indicaram elevada contribuição europeia (superior a 70%) e baixa contribuição ameríndia (inferior a 10%) na população, enquanto que as análises de mistura individual se mostraram consistentes, com a maioria dos indivíduos apresentando elevada ancestralidade europeia. Os resultados dos marcadores relativos ao sexo (Amelogenina, Y-INDEL e DYS391) foram consistentes com o sexo dos doadores das amostras. As frequências alélicas e parâmetros forenses foram calculados para os STRs, revelando uma alta informatividade. A Probabilidade de Match combinada e o Poder de Exclusão combinado foram de 1,19 x 10-36 e 0,999999999997 respectivamente. Dos 29 STRs autossômicos presentes, seis apresentaram desvios ao equilíbrio de Hardy-Weinberg, refletindo possíveis falhas no sequenciamento e genotipagem destes marcadores / The field of forensic genetics has developed increasingly with the implementation of new sets of DNA markers with higher levels of informativeness. The genetic markers are widely used in human identification as they allow distinguishing individuals with high accuracy. Two of the most commonly used markers are the Short Tandem Repeats (STRs) and the Single Nucleotide Polymorphisms (SNPs). Newer kits such as GlobalFiler (Thermo Fisher Scientific) and PowerPlex Fusion System (Promega) can analyze more than 20 STRs loci at once. When comparing with STRs, the SNPs are less informative and many more loci are needed to reach the same informativeness of STR kits. However, they are advantageous when using degraded DNA samples. The identification sets such as the 52-plex developed by the SNPforID Consortium and the IISNPs have been analyzed in many worldwide populations. With the development of next generation sequencing techniques (NGS Next Generation Sequencing), obtaining DNA profiles has become more accurate and some platforms allow generating profiles of up to 96 individuals simultaneously. The main goal of this study is to analyze 171 markers (Amelogenin, Y-INDEL, 30 STRs and 139 SNPs) in 340 admixed individuals from Ribeirão Preto, SP, using the NGS platform MiSeq Personal Sequencer (Illumina Inc.). This will allow the calculation of allele and genotype frequencies, the verification of adherence to Hardy-Weinbergs equilibrium and the estimation of forensic parameters for each set of marker. Ancestry analysis was performed for the sets of SNPs. The HaloPlex kit (Agilent Technologies, Inc) was used for library preparation including the STRs from the kits GlobalFiler and PowerPlex Fusion System and the SNPs from the SNPforID consortium (52-plex) and IISNPs (92 SNPs) identification sets. A single SNP (rs763869) from the SNPforID set was not analyzed due to technical issues. Only six of the 139 analyzed SNPs presented significant deviation from the Hardy-Weinberg equilibrium expectations, which is expected by chance alone. The SNPs sets exhibited high informativeness, with matchprobability ranging from 6.48 x 10-21 (52-plex) to 4.91 x 10-38 (IISNPs) and exclusion power of 0.9997 (52-plex) and 0.99999997 (IISNPs). In general, ancestry estimates obtained using these sets indicated a high European contribution (higher than 70%) and low Amerindian contribution (less than 10%) in the population sample, while the individual admixture analyses exhibited were highly consistent, with the majority of individuals presenting high European ancestry. The results of the sex markers (Amelogenin, Y-INDEL and DYS391) were in agreement with the reported sexes from sample donors. The allele frequencies and forensic parameters calculated for the STRs revealed high informativeness. The combined match probability and the combined exclusion power were 1.19 x 10-36 and 0.999999999997 respectively. Six of the 29 autosomal STRs presented significant deviations from the HardyWeinberg equilibrium expectations, reflecting possible failures in sequencing and genotyping of these markers

Made available in DSpace on 2016-01-26T12:51:30Z (GMT). No. of bitstreams: 1 nataliaguelfifurlani_dissert.pdf: 2586696 bytes, checksum: c66f56a5e70e155d3ec22d8e0643f53a (MD5) Previous issue date: 2011-07-27 / The Brazilian population is mainly composed of three parental populations: Native Americans, Europeans and Africans. Significant levels of tri-hybrid admixture have been detected in all regions and socioeconomic levels within the country. Recent statistical methods allied to the ability to genotype a large number of markers permit the estimate of the admixture at the individual level. In epidemiological studies with case-control design, ethnic heterogeneity between subgroups can produce false positive results. Therefore, for this type of study, it is important to evaluate individual admixture, as well as to measureits influence on the genetic structure of diverse subgroups within the Brazilian populations. Ancestry Informative Markers (AIMs), which frequencies show large differences between parental populations are suitable for tracking the effect of mixing, in order to avoid spurious associations in case control studies. This knowledge could help to further define the levels of population structure in groups and subgroups that constitute the subject of epidemiological studies, optimizing their designto avoid false positive results. Among these groups are particularly relevant studies addressing genetic factors that modulate susceptibility to malaria in regions where the population is exposed to endemic levels, for example, those residing in the municipality of Porto Velho (RO), Brazilian amazon region and surroundings. Objectives: a) to describe the Amerindian, European and African individual genomic ancestry in healthy individuals and patients with falciparum malaria in Porto Velho, RO (Western Amazonia) and assess its impact on the design of epidemiological studies and b) to determine, from the genotyped markers, the genetic structure of populations of falciparum malaria patients and healthy individuals from the same region, depending on the admixture levels . / A população brasileira é formada majoritariamente por três populações parentais: Nativos Americanos, Europeus e Africanos. Níveis significativos de miscigenação tri-híbrida já foram detectados em todas as regiões e níveis sócio-econômicos do País. Métodos estatísticos recentes aliados à possibilidade de genotipagem de um grande número de marcadores permitem estimar a miscigenação em nível individual. Em estudos epidemiológicos com desenho de caso-controle, a heterogeneidade étnica entre estas categorias pode produzir resultados falso-positivos. Por este motivo, para este tipo de estudo, é importante estudar a miscigenação individual, assim como avaliar como a miscigenação neste nível influencia a estrutura genética dos diferentes subgrupos das populações brasileiras. O controle do efeito da miscigenação, para evitar as associações espúrias em estudos do tipo caso-controle pode ser feito estudando Marcadores Informativos de Ancestralidade (MIAs), os quais apresentam grandes diferenças de freqüência entre as populações parentais. Este conhecimento poderá contribuir para a futura definição dos níveis de estruturação populacional em grupos e subgrupos que constituirão alvo de estudos epidemiológicos, permitindo a otimização dos mesmos, a fim de evitar resultados falso-positivos. Dentre estes grupos, são de particular relevância estudos que abordem os fatores genéticos que modulam a suscetibilidade à malária em regiões onde a população se encontra exposta em nível endêmico como, por exemplo, a que reside no município de Porto Velho (RO) e região. Objetivos: a) descrever a ancestralidade genômica individual Ameríndia, Européia e Africana em indivíduos sadios e portadores de malária por Plasmodium falciparum da cidade de Porto Velho, RO (Amazônia Ocidental), Brasil, e avaliar seu impacto no desenho de estudos epidemiológicos e b) determinar, a partir dos marcadores genotipados, a estrutura genética das populações de portadores de malária falciparum e indivíduos sadios da mesma região, em função dos níveis de miscigenação.

Introdução: Hipertensão é um dos principais fatores de risco para diversas doenças cardiovasculares agudas e crônicas, morte prematura e incapacidade. Há evidências de que seja mais prevalente e grave em indivíduos negros do que em brancos, porém os mecanismos que contribuem para essa diferença não são totalmente compreendidos. Todavia, fatores socioeconômicos, situação de discriminação racial e exclusão social podem influenciar fortemente a frequência, distribuição e causalidade das doenças mais incidentes entre a população brasileira afrodescendente, entre elas, a hipertensão. Nesse contexto, merecem atenção as comunidades quilombolas, que são núcleos populacionais de afrodescendentes, marcados por processos de discriminação e exclusão que imprimem em sua realidade um quadro socioeconômico bastante excludente em relação à população brasileira de modo geral. São escassos na literatura estudos que caracterizem sua situação de saúde. Tendo em vista o contexto de vulnerabilidade social e a magnitude que representa a hipertensão, entende-se que todos os esforços devem ser feitos a fim de viabilizar estudos direcionados ao conhecimento desse agravo na população de remanescentes de quilombolas do Rio Grande do Sul (RS). OBJETIVO: Identificar a prevalência e fatores associados à hipertensão arterial em adultos residentes em comunidades quilombolas do RS. MÉTODOS: Estudo transversal de base populacional, realizado em 2011 com adultos responsáveis por domicílios de comunidades quilombolas do RS. Foram selecionadas 634 famílias por amostragem proporcional ao tamanho, de 22 comunidades localizadas em 17 municípios gaúchos. O desfecho foi obtido através da pergunta: “Algum médico já lhe disse que você tem hipertensão (pressão alta)?”. Associações entre desfecho e variáveis explanatórias (demográficas, socioeconômicas, estilo de vida e de saúde) foram analisadas por regressão de Poisson, com variância robusta e entrada hierarquizada das variáveis. Por fim, foram calculadas as frações atribuíveis populacionais por componente (FAPC) para os fatores modificáveis associados à hipertensão. RESULTADOS: Foram entrevistados 589 adultos. Houve perda de 7% nas entrevistas em relação à amostra originalmente prevista. A maioria era do sexo feminino (64,9%), residia no perímetro rural (81,7%) era da raça/cor não branca (90,7%), recebia até ½ salário mínimo (63,3%) e 80% tinha menos de 8 anos de estudo. A média de idade foi de 45 anos (DP 17). 38,3% (IC95% 31,4%-45,1%) dos entrevistados referiu diagnóstico de hipertensão. Análise multivariada revelou associação com consumo excessivo de álcool (RP 0,52; IC95% 0,31-0,85), circunferência da cintura acima do adequado (RP 1,74; IC95% 1,41-2,15) e presença de diabetes (RP 1,38; IC95% 1,17-1,64). Idade apresentou associação direta e escolaridade mostrou-se inversamente associada à hipertensão. A análise da FAPC revelou que se os indivíduos tivessem 8 anos ou mais de estudo a prevalência de hipertensão arterial seria reduzida em 22,5%. CONCLUSÕES: A prevalência de hipertensão observada nas comunidades quilombolas do RS foi elevada. Cabe salientar a situação de vulnerabilidade dessa população, evidenciada, ao menos em parte, pela baixa escolaridade (80% sem ensino fundamental completo), baixa renda (63,3% recebem menos de ½ salário mínimo), grau de isolamento (81,7% residem em áreas isoladas do perímetro rural) e pelo fato de 90,7% da amostra ser da raça/cor não branca, o que provavelmente sujeita esses indivíduos a sofrerem discriminação racial e suas consequências adversas. Considerando-se a magnitude que representa a hipertensão e a extrema vulnerabilidade social desses grupos, políticas públicas que garantam seu acesso a direitos fundamentais (saúde, renda e escolaridade) poderiam ter impacto importante na diminuição da prevalência de hipertensão. / INTRODUCTION: Hypertension is a major risk factor for many acute and chronic cardiovascular diseases, premature death and disability. There is evidence that it is more prevalent and severe in black than in white populations, but the contributing mechanisms to this difference are not totally understood yet. However, socioeconomic factors, racial discrimination and social exclusion situations are strongly related to the frequency, distribution and causality of chronic diseases among the Afro-descendant Brazilian populations, including hypertension. In this context, quilombola communities deserve special attention. Quilombolas are settlements of African descendants, marked by discrimination and exclusion processes, printing an exclusionary socio-economic framework in their reality when compared to the Brazilian population in general. There are just a few studies in the literature that characterize their health status. Given their social vulnerability context and the important risk offered by high blood pressure, it is clear that an effort has to be made in order to enhance the knowledge about this disease in the quilombola population in Rio Grande do Sul state (RS). OBJECTIVE: To identify the prevalence of factors associated to arterial hypertension in household adults, residing in quilombola communities in Rio Grande do Sul state, Brazil. METHODS: Cross-sectional population-based study, conducted in 2011 with adult households in quilombola communities in the state of RS. We selected 634 families of 22 communities located in 17 RS municipalities, by sampling proportional to the size. The outcome was obtained by the question: “Has a doctor ever told you that you have hypertension (high blood pressure)?". Associations between the outcome and explanatory variables (demographic, socioeconomic, health and life style) were analyzed by Poisson regression, using robust variance and hierarchical input variables. The population attributable fractions were calculated by component (PAFC) for modifiable factors associated to hypertension. RESULTS: We interviewed 589 adults. Most women (64,9%), from the rural perimeter (81,7%), race/color non-white (90,7%), earning up to ½ minimum wage (63,3%) and 80% had less than 8 years of study. The average age was 45 years (SD 17). Hypertension diagnosis was reported by 38,3% (95% CI 31,4% - 45,1%) of the respondents. Multivariate analysis revealed an association with excessive alcohol consumption (OR 0,52, 95% CI 0,31 to 0,85), circumference of the waist above the recommended limit (PR 1,74, 95% CI 1.41 to 2,15) and presence diabetes (OR 1,38, 95% CI 1,17 to 1,64). Age had a direct association and educational level was inversely associated with hypertension. The PAFC analysis revealed that among individuals with eight years or more of study, the prevalence of hypertension was reduced by 22,5%. PAFC analysis revealed that for individuals with eight or more years of formal education, the prevalence of high blood pressure would be reduced by 22,5%. CONCLUSIONS: The prevalence of hypertension in the quilombola communities of RS is high. We emphasize the vulnerability of this population, evidenced by low educational levels, low income, geographical isolation and to the fact that 90,7% of the sample is non-white, subjecting these individuals to racial discrimination and its adverse consequences. Considering the magnitude of hypertension and the extreme social vulnerability of these groups, public policies that guarantee their access to fundamental rights (health, income and education) could have an remarkable impact in reducing the prevalence of hypertension.

A convenience sample of 184 first-time childbearing women was recruited from two public hospitals with one hospital randomly selected as the experimental group. The experimental group (n = 92) received the childbirth psychoeducation programme and routine childbirth education. The comparison group (n = 92) received the routine childbirth education only. / Outcomes on learned resourcefulness, maternal role competence and perinatal depression were measured by C-SCS, C-PSOC (Efficacy Subscale) and Edinburgh Postnatal Depression Scale (EPDS), respectively, at baseline, immediately post-intervention, six weeks and six months postpartum. Maternal role satisfaction was assessed at six weeks and six months postpartum using C-PSOC (Satisfaction Subscale). Doubly multivariate analysis of covariance was performed to compare the effects of childbirth psychoeducation programme between the experimental and comparison groups. In addition, 16 participants in the experimental group were interviewed at six weeks postpartum to explore their perceived impacts of childbirth psychoeducation programme in helping them cope with the experience of new motherhood. Content analysis was used to analyze the interview data. / Results of the phase I study indicated good psychometric properties of C-SCS and C-PSOC in Chinese childbearing women. Results in the phase II study revealed significant improvement in learned resourcefulness at six weeks postpartum (p = 0.004), and overall reduction in depressive symptoms (p = 0.01) for women receiving the childbirth psychoeducation programme compared with the routine childbirth education group after adjusting for baseline group differences on age and social support. No significant change was detected on maternal role competence. However, women receiving the childbirth psychoeducation programl1'l;e had significantly higher level of satisfaction in the maternal role at six weeks postpartum (p = 0.01). / The crisis nature of early motherhood, the frequent feeling of incompetence in the maternal role, the increasing evidence of postpartum depression in the Chinese population, coupled with the changing nature of socio-cultural environment challenge midwives to make continued refinement of childbirth education to enhance women's adjustment during the transition to motherhood. Learned resourcefulness has been identified as an important coping repertoire that promotes healthy adjustment in the perinatal period. The aim of this study was to determine the effectiveness of a childbirth psychoeducation programme based on the concept of learned resourcefulness. / The qualitative interviews revealed that the experimental group perceived the childbirth psychoeducation programme to be helpful in increasing their confidence in the maternal role, improving their emotional well-being and fostering the development of learned resourcefulness skills. The findings of this study support the effectiveness of childbirth psychoeducation programme based on the concept of learned resourcefulness for reducing depressive symptoms in first-time Chinese childbearing women, and highlight the contributions midwives can make to continue improving the quality of childbirth education in Chinese society. / The study had two phases. The first phase aimed at establishing the psychometric properties of the Chinese versions of Self-Control Schedule (C-SCS) and Parenting Sense of Competence Scale (C-PSOC), which were used as outcome measures in the second phase. The second phase adopted a pretest-posttest, control group quasi-experimental design to examine the effects of a childbirth psychoeducation programme on learned resourcefulness, maternal role competence and satisfaction, and perinatal depression. / Ngai Fei Wan. / Adviser: W. Y. Ip. / Source: Dissertation Abstracts International, Volume: 72-11, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 259-300). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese; some appendices in Chinese.

Conclusions. The growing epidemic of type 2 diabetes and its cardiorenal complications place a major burden on our health care system. Diabetic kidney disease is of particular importance in Asian populations including Chinese. In this series of studies, using a large prospective cohort established since 1995, I confirmed the powerful predictive value of albuminuria on cardio-renal complications. Inhibition of the RAAS interacted with both modifiable and genetic factors, notably the ACE I/D polymorphism, on the development of cardio-renal complications. In addition, it was found that CKD predicts CVD independent of albuminuria. Based on two prospective studies, I confirmed the effectiveness of global risk-factor control using structured care protocol to prevent these devastating complications. (Abstract shortened by UMI.) / I then examined the possible independent and interactive effects of CKD and albuminuria on cardio-renal outcomes in the original cohort of 5,004 patients. Glomerular filtration rate was estimated (eGFR) by the Modification of Diet in Renal Disease equation. The frequency of CKD as defined by eGFR <60ml/min/1.73m 2 was 15.8% in the cohort at baseline, when 6% of patients had serum creatinine ≥150mumol/L. / In collaboration with colleagues, I have conducted a series of studies to examine the prognostic factors for cardio-renal complications in Chinese type 2 diabetic patients. The modulating effects of RAAS inhibition and the effectiveness of rnuitidisciplinary care to prevent ESRD are also examined. / Research Hypotheses. (1) Albuminuria is a prognostic factor on cardio-renal outcomes in type 2 diabetes patients; (2) Chronic Kidney Disease is associated with other metabolic risk factors and phenotypes and is a prognostic factor on cardio-renal outcomes in type 2 diabetes patients; (3) Angiotensin-converting-enzyme insertion/deletion polymorphism is a prognostic factor on cardio-renal outcomes in type 2 diabetes patients, and has an effect on treatment responses with RAAS blockage with ACE inhibitors; (4) Structured care models by risk stratification using various prognostic factors and adherence to care protocol can improve cardio-renal outcome in type 2 diabetes patients. / Results. In a prospective cohort of 5,004 patients, I examined the effect of albuminuria and ACE inhibition on survival and cardio-renal outcomes in 3,773 patients who had been observed for at least 6 months with a mean follow up period of 35.8 months. / Taken together, measurement of serum creatinine alone without GFR estimation may underestimate the frequency of CKD in Chinese type 2 diabetic patients. Estimated GFR was inversely associated wit-29h an increasing frequency of micro- and macrovascular complications cross-sectionally and an increased risk of all-cause mortality prospectively, independent of albuminuria and metabolic control. / So Wing Yee. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3422. / Thesis (M.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 203-243). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-12-06T17:23:43Z No. of bitstreams: 1 NataliaMandarino.pdf: 1259793 bytes, checksum: 4c22457bb7148f23dd689ff0d6e19abc (MD5) / Made available in DSpace on 2017-12-06T17:23:43Z (GMT). No. of bitstreams: 1 NataliaMandarino.pdf: 1259793 bytes, checksum: 4c22457bb7148f23dd689ff0d6e19abc (MD5) Previous issue date: 2017-09-05 / FAPEMA / The role of vitamin D in the regulation of bone metabolism is already well established. However, in recent years, the role of vitamin D in extraskeletal health has been widely explored. In the cardiovascular area, vitamin D deficiency has been independently associated with the occurrence of myocardial infarction, stroke and cardiovascular death. The mechanisms to explain the association between hypovitaminosis D and cardiovascular disease are still not fully understood, and their association with atherosclerosis is postulated. However, studies attempting to correlate hypovitaminosis D with atherosclerosis markers have produced conflicting results, in the same way as small randomized trials of oral supplementation to evaluate intermediate outcomes, so there is currently considerable debate about whether hypovitaminosis D represents a new risk or would be just an inflammatory marker. In the first article, a comprehensive review was made of the role of vitamin D deficiency in the pathogenesis of cardiovascular disease, from basic aspects of its biosynthesis to the results of interventional studies, through its oral supplementation. The second article presents the results of a cross - sectional analysis of 382 individuals living in quilombola communities in Alcântara - MA, participants of the PREVRENAL cohort, presenting at least one cardiovascular risk factor, with a mean age of 57.79 (± 15.3) years and a slight predominance, in which the serum levels of 25-hydroxyvitamin D, the stable circulating form of the vitamin, were correlated with an established marker of subclinical atherosclerosis, carotid intima-media thickness, and other cardiovascular risk factors. Socio-demographic, lifestyle, anthropometric and clinical data were collected and biochemical tests were performed, including the dosage of 25-hydroxyvitamin D by means of the electrochemiluminescence assay. The urinary excretion of albumin was evaluated by means of the albumin / creatinine ratio in an isolated sample of urine. Hypovitaminosis D was defined as serum 25- hydroxyvitamin D levels <30 ng / mL. All participants underwent examination of the common carotid arteries by high-resolution ultrasonography to measure the intimamedia thickness, and the mean of the measurements on both sides was adopted. Serum levels of 25-hydroxyvitamin D were 50.4 (± 13.5) ng / mL, with a low prevalence of hypovitaminosis D (<5%). By simple linear correlation, there was a significant inverse association between 25-hydroxyvitamin D levels and carotid intima-media thickness (r = -0.174, p = 0.001). However, after multiple regression analysis, only the variables male gender, age, smoking, systolic blood pressure, fasting blood glucose and LDL-cholesterol remained significantly associated with carotid intima-media thickness. Levels of 25-hydroxyvitamin D were independently associated positively with HDL-cholesterol and inversely with urinary albumin excretion. In conclusion, in this Afrodescendant population, with a low prevalence of hypovitaminosis D, there was no independent association between serum 25- hydroxyvitamin D levels and carotid intima-media thickness, a finding that contradicts the hypothesis of its antiatherosclerotic role. On the other hand, its positive association with HDL-cholesterol and the inverse association with urinary albumin excretion, also considered as an independent predictor of cardiovascular events, does not allow the exclusion of cardiovascular protection actions of the vitamin in this population profile. / O papel da vitamina D na regulação do metabolismo ósseo já está bem estabelecido. Entretanto, nos últimos anos, o papel da vitamina D na saúde extraesquelética tem sido amplamente explorado. Na área cardiovascular, a deficiência de vitamina D tem sido associada de forma independente à ocorrência de infarto do miocárdio, acidente vascular cerebral e morte cardiovascular. Os mecanismos para explicar a associação entre hipovitaminose D e doença cardiovascular ainda não estão de todo esclarecidos, sendo postulada sua vinculação com a aterosclerose. No entanto, estudos procurando correlacionar hipovitaminose D com marcadores de aterosclerose têm produzido resultados conflitantes, da mesma forma que pequenos estudos randomizados de suplementação oral para avaliar desfechos intermediários, de modo que há atualmente considerável debate acerca de se a hipovitaminose D representa um novo fator de risco ou seria apenas um marcador inflamatório. No primeiro artigo, já publicado, procurou-se realizar uma revisão abrangente sobre o papel da deficiência de vitamina D na patogenia da doença cardiovascular, incluindo desde aspectos básicos de sua biossíntese até os resultados de estudos de intervenção, por meio de sua suplementação oral. O segundo artigo apresenta os resultados de uma análise transversal de 382 indivíduos habitantes de comunidades quilombolas em Alcântara - MA, participantes da coorte PREVRENAL, apresentando pelo menos um fator de risco cardiovascular, com média de idade de 57.79 (± 15.3) anos e discreto predomínio do sexo feminino, em que se procurou correlacionar os níveis séricos de 25-hidroxivitamina D, a forma circulante estável da vitamina, com um marcador estabelecido de aterosclerose subclinica, a espessura médio-intimal carotídea, e outros fatores de risco cardiovascular. Foram coletados dados sócio-demográficos, sobre estilo de vida, antropométricos e clínicos e realizados exames bioquímicos, incluindo a dosagem de 25-hidroxivitamina D, por meio do ensaio eletroquimioluminiscência. A excreção urinária de albumina foi avaliada por meio da razão albumina / creatinina em amostra isolada de urina. Hipovitaminose D foi definida como níveis séricos de 25-hidroxivitamina D <30 ng / mL. Todos os participantes foram submetidos a exame das artérias carótidas comuns por ultrassonografia de alta resolução para medida da espessura médio-intimal, sendo adotada a média das medidas de ambos os lados. A média dos níveis séricos de 25-hidroxivitamina D foi de 50.4 (± 13.5) ng / mL, observando-se uma baixa prevalência de hipovitaminose D (<5%). Por correlação linear simples, observou-se uma associação inversa significativa entre os níveis de 25-hidroxivitamina D e a espessura médio-intimal carotídea (r = -0.174, p = 0.001). Entretanto, após análise de regressão múltipla, apenas as variáveis sexo masculino, idade, tabagismo, pressão arterial sistólica, glicemia em jejum e LDL-colesterol permaneceram significativamente associadas com a espessura médio-intimal carotídea. Níveis de 25-hidroxivitamina D se associaram independentemente, de forma positiva com o HDL-colesterol, e inversa com a excreção urinária de albumina. Em conclusão, nesta população afrodescendente, com baixa prevalência de hipovitaminose D, não se observou uma associação independente entre os níveis séricos de 25- hidroxivitamina D e a espessura médio-intimal carotídea, achado que contraria a hipótese do seu papel antiaterosclerótico. Por outro lado, a sua associação positiva com o HDL-colesterol e inversa com a excreção urinária de albumina, também considerada um preditor independente de eventos cardiovasculares, não permite afastar ações de proteção cardiovascular da vitamina neste perfil populacional.

Although the clinical efficacy of statins has been well established, there is a wide inter-individual variation in the lipid responses to statins. Pharmacogenetic studies have identified some genetic differences that contribute to the variation, but overall the results have been disappointing. The studies described in this thesis were performed to examine whether certain genetic variants predicted the lipid responses to rosuvastatin in Chinese patients. Over 400 Chinese patients with increased risk of cardiovascular disease (CVD) who were treated with rosuvastatin 10 mg daily for at least 4 weeks (more than 97% of patients had at least 6 weeks treatment) were studied, including 166 having familial hypercholesterolaemia (FH) and 36 having rheumatoid arthritis (RA). They were genotyped for 135 polymorphisms in 62 candidate genes/loci potentially related to pharmacokinetics or pharmacodynamics of statins and lipid metabolism. Associations between genetic polymorphisms and the lipid responses to rosuvastatin were analyzed in 386 patients with good compliance. The associations between genetic polymorphisms and some risk factors for CVD including baseline lipid levels, high-sensitivity C-reactive protein (hsCRP), uric acid and bilirubin levels were also analyzed. / Some novel genetic determinants of the LDL-C response to rosuvastatin treatment have been identified in this study. The responses in HDL-C and triglycerides were related more closely to the baseline levels of these lipids than to any of the polymorphisms examined. Genetic associations with baseline lipid parameters, hsCRP, uric acid and bilirubin were identified and generally correspond with some of the previous reports of studies in Chinese and other ethnic groups. / The key findings of the study are as follows: 1. The polymorphisms most highly associated with the low-density lipoprotein cholesterol (LDL-C) response were 421C>A in the ATP-binding cassette G2 (ABCG2) gene (P=9.2x10 -7), followed by 18281G>A (V257M) in the flavin-containing monooxygenase 3 (FMO3) gene (P=0.0002), 1421C>G in the lipoprotein lipase (LPL) gene (P=0.002), and rs4420638 in the apolipoprotein E/C-I/C-IV/C-II (APOE/C1/C4/C2) gene cluster (P=0.004). These genetic polymorphisms and having FH totally explained 13.6% of the variance in percentage change in LDL-C in response to rosuvastatin. The greater percentage reduction in LDL-C in patients with the ABCG2 421AA genotype compared to those with the ABCG2 421CC genotype was equivalent to at least doubling the dose of rosuvastatin. 2. Three SNPs (glucokinase regulator [ GCKR] rs1260326, apolipoprotein AS [APOA5] -1131T>C and the solute carrier organic anion transporter 1B1 [SLCO1B1] 521T>C) tended to be associated with percentage changes in high-density lipoprotein cholesterol (HDL-C) (P&lt;0.05), but none of these reached the overall significance level. In multivariate stepwise regression analysis, baseline HDL-C (P=1.6x10 -6), having diabetes (P=0.0004) or RA (P=0.002) and the SLCO1B1 521T>C polymorphism (P=0.03) were determinants of HDL-C responses, contributing 9.9% of the variance in percentage change in HDL-C, but the genetic factors only contributed to 0.8% of the variance. 3. The triglyceride response to rosuvastatin was highly variable and was strongly related to baseline levels. The diacylglycerol acyltransferase-2 (DGAT2) rs10899113 C>T polymorphism tended to be associated with reduced triglyceride response in a gene-dose dependent manner. However, in multivariate stepwise regression analysis, baseline triglyceride level was the only factor that strongly related to the triglyceride response, explaining 14.4% of the variance. 4. This study has also analyzed relationships between on-treatment plasma hsCRP concentrations and cardiovascular risk factors and 14 single nucleotide polymorphisms in CRP and other candidate genes, which showed that central obesity, low HDL-C and CRP polymorphisms are major determinants of higher hsCRP levels in Chinese patients on treatment with rosuvastatin. 5. The association between genetic polymorphisms and lipid traits were analyzed in FH and non-FH patients separately due to their different lipid profiles. The analysis has shown that there were different genetic predictors of lipid levels in patients with and without FH and that more genetic factors appeared to affect the baseline lipid levels in patients with FH compared to non-FH patients, suggesting complex interactions between genetic and environmental factors and plasma cholesterol levels in patients with and without FH. 6. The SLC2A9 (solute carrier family 2, member 9) rs1014290 T>C was significantly associated with plasma uric acid levels in a gene-dose dependent manner (P=1.0x10-5) and the relationship was more pronounced in women or in patients without hypertension than in men or patients with hypertension. The ABCG2 421 C>A did not show a significant effect on uric acid levels. 7. The UGT1A1 (uridine diphosphate glucuronosyltransferases family, polypeptide A1) variants *28 (P=1.5x10 -9) and *6 (P=2.2x10-7) were independently associated with increased baseline bilirubin levels. Polymorphisms in SLCO1B1 did not appear to affect bilirubin levels in this study. / Hu, Miao. / Adviser: Brian Tomlinson. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 230-264). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Jiang, Jieying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 170-186). / Abstract also in Chinese. / ACKNOWLEDGEMENT --- p.II / ABBREVIATIONS --- p.III / ABSTRACT OF THESIS ENTITLED: --- p.VI / 摘要 --- p.IX / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Individual variations of blood sex steroid levels and their determinants --- p.1 / Chapter 1.1.1 --- Introduction to Sex steroids --- p.1 / Chapter 1.1.2 --- Androgens --- p.1 / Chapter 1.1.2.1 --- Types of androgens --- p.1 / Chapter 1.1.2.2 --- Androgens plasma concentration and relative biological potencies --- p.2 / Chapter 1.1.2.3 --- Androgen biosynthesis and metabolism --- p.3 / Chapter 1.1.2.4 --- Testosterone transportation in plasma --- p.6 / Chapter 1.1.2.5 --- Measurement of free testosterone --- p.7 / Chapter 1.1.2.6 --- The hypothalamus-pituitary-testicular axis and testosterone secretion --- p.8 / Chapter 1.1.2.7 --- Androgen action --- p.10 / Chapter 1.1.2.8 --- Androgen biological function and diseases in men --- p.11 / Chapter 1.1.3 --- Estrogen biological function and diseases in men --- p.12 / Chapter 1.1.4 --- Factors influencing circulating sex steroid levels --- p.13 / Chapter 1.1.4.1 --- Genetic determinants affecting sex steroid levels --- p.15 / Chapter 1.2 --- Genetic variants in sex steroid metabolic pathway and hepatocellular carcinoma (HCC) --- p.18 / Chapter 1.2.1 --- Epidemiology of HCC --- p.18 / Chapter 1.2.2 --- Etiological factors of HCC --- p.22 / Chapter 1.2.3 --- The male predominance in HCC --- p.24 / Chapter 1.2.4 --- Genetic predisposition to HCC --- p.26 / Chapter CHAPTER 2 --- PART A STUDY: GENETIC VARIATIONS IN SEX STEROID METABOLIC PATHWAY AND ASSOCIATION WITH SEX STEROID LEVELS --- p.28 / Chapter 2.1 --- Introduction --- p.28 / Chapter 2.1.1 --- Candidate genes association with sex steroid levels --- p.28 / Chapter 2.1.2 --- Genes involved in androgen metabolism --- p.29 / Chapter 2.1.2.1 --- SRD5A --- p.29 / Chapter 2.1.2.2 --- HSD3B1 --- p.30 / Chapter 2.1.2.3 --- HSD17B2 --- p.31 / Chapter 2.1.2.4 --- AKR1C3 and AKRlC4 --- p.31 / Chapter 2.1.2.5 --- AKR1D1 --- p.32 / Chapter 2.1.3 --- Genes involved in estrogen metabolism --- p.32 / Chapter 2.1.3.1 --- CYP19A1 --- p.32 / Chapter 2.1.3.2 --- Other genes involved in estrogen metabolism --- p.33 / Chapter 2.1.4 --- Association of sex steroid related genes and blood concentrations of sex steroid levels --- p.33 / Chapter 2.1.4.1 --- Genes involved in androgen metabolic pathway and association with sex steroid levels --- p.33 / Chapter 2.1.4.2 --- Genes involved in estrogen metabolic pathway and association with sex steroid levels --- p.36 / Chapter 2.1.5 --- Aims of the study (Part A) --- p.37 / Chapter 2.2 --- Materials and methods --- p.38 / Chapter 2.2.1 --- Study subjects and biological samples --- p.38 / Chapter 2.2.2 --- TagSNP selection --- p.39 / Chapter 2.2.3 --- Genotyping of tagging SNPs --- p.41 / Chapter 2.2.4 --- Genotyping methods comparison --- p.52 / Chapter 2.2.5 --- Statistics --- p.53 / Chapter 2.3 --- Results --- p.54 / Chapter 2.3.1 --- Characteristics of study population --- p.54 / Chapter 2.3.2 --- Replication study for the association of CYP19A1 --- p.55 / Chapter 2.3.2.1 --- Association of the SNP rs2470152 and rs2899470 with serum estrogen and testosterone levels --- p.55 / Chapter 2.3.2.2 --- Halotype analysis and haplotype association in the tertile groups --- p.61 / Chapter 2.3.2.3 --- Haplotype construction of 3 SNPs --- p.63 / Chapter 2.3.3 --- SRD5A1 --- p.65 / Chapter 2.3.3.1 --- Association of SRD5A1 and sex steroid levels --- p.65 / Chapter 2.3.3.2 --- Haplotype analysis and haplotype association in the tertile groups --- p.71 / Chapter 2.3.4 --- SRD5A2 --- p.72 / Chapter 2.3.4.1 --- Association of SRD5A2 and sex steroid levels --- p.72 / Chapter 2.3.4.2 --- Haplotype association analysis of SRD5A2 in tertile groups --- p.76 / Chapter 2.3.5 --- HSD3B1 --- p.77 / Chapter 2.3.5.1 --- Association of HSD3B1 and sex steroid levels --- p.77 / Chapter 2.3.6 --- HSD17B2 --- p.80 / Chapter 2.3.6.1 --- Association of HSD17B2 and sex steroid levels --- p.80 / Chapter 2.3.6.2 --- Halotype association analysis of HSD17B2 in the tertile groups --- p.87 / Chapter 2.3.7 --- AKR1C4 --- p.89 / Chapter 2.3.7.1 --- Association of AKR1C4 and sex steroid levels --- p.89 / Chapter 2.3.7.2 --- Halotype association analysis of AKR1C4 in the tertile groups --- p.93 / Chapter 2.3.8 --- AKR1D1 --- p.94 / Chapter 2.3.8.1 --- Association of AKR1D1 and sex steroid levels --- p.94 / Chapter 2.3.8.2 --- Haplotype association analysis of AKR1D1 in the tertile groups --- p.99 / Chapter 2.3.9 --- AKR1C3 --- p.100 / Chapter 2.3.9.1 --- Association of AKR1C3 and sex steroid levels --- p.100 / Chapter 2.3.9.2 --- Haplotype association analysis of AKR1C3 in the tertile groups --- p.104 / Chapter 2.3.10 --- Overall association of polymorphisms in sex steroid metabolism genes and metabolites levels in blood --- p.105 / Chapter 2.4 --- Discussion --- p.106 / Chapter 2.4.1 --- SRD5A and sex steroid levels --- p.106 / Chapter 2.4.2 --- HSD17B2 and sex steroid levels --- p.110 / Chapter 2.4.3 --- "AKR1D1, AKR1C4, AKR1C3 and catabolic intermediates of sex steroids" --- p.112 / Chapter 2.4.4 --- HSD3B1 and sex steroid levels --- p.114 / Chapter 2.4.4 --- CYP19A1 and sex steroid levels --- p.114 / Chapter CHAPTER 3 --- PART B STUDY: GENETIC VARIATIONS IN SEX STEROID METABOLIC PATHWAY AND ASSOCIATION WITH HCC --- p.119 / Chapter 3.1 --- Introduction --- p.119 / Chapter 3.1.1 --- Previous genetic association studies of HCC on sex steroid metabolic pathways --- p.119 / Chapter 3.1.2 --- Previous genetic association studies of HCC in other pathways --- p.120 / Chapter 3.1.3 --- "Association of sex steroid related genes and other cancers, like prostate cancer" --- p.121 / Chapter 3.1.4 --- Aims of the study (Part B) --- p.123 / Chapter 3.2 --- Materials and method --- p.125 / Chapter 3.2.1 --- "Study subjects, Genomic DNA extraction" --- p.125 / Chapter 3.2.2 --- Tissue specimen and cell lines --- p.125 / Chapter 3.2.3 --- TagSNP selection --- p.126 / Chapter 3.2.4 --- Genotyping of tagging SNPs --- p.126 / Chapter 3.2.5 --- Statistics --- p.127 / Chapter 3.2.6 --- Extraction of RNA and Reverse-Transcription-PCR --- p.128 / Chapter 3.3 --- Results --- p.130 / Chapter 3.3.1 --- SRD5A1 --- p.130 / Chapter 3.3.1.1 --- SRD5A1 polymorphisms and risk of HCC --- p.130 / Chapter 3.3.2 --- SRD5A2 --- p.134 / Chapter 3.3.2.1 --- SRD5A2 polymorphisms and risk of HCC --- p.134 / Chapter 3.3.2.2 --- Haplotype analysis --- p.136 / Chapter 3.3.3 --- HSD3B1 --- p.137 / Chapter 3.3.3.1 --- HSD3B1 polymorphisms and risk of HCC --- p.137 / Chapter 3.3.3.2 --- Haplotype analysis --- p.139 / Chapter 3.3.4 --- HSD17B2 --- p.140 / Chapter 3.3.4.1 --- HSD17B2 polymorphisms and risk of HCC --- p.140 / Chapter 3.3.4.2 --- Haplotype analysis --- p.143 / Chapter 3.3.5 --- CYP19A1 --- p.144 / Chapter 3.3.5.1 --- CYP19A1 polymorphisms and risk of HCC --- p.144 / Chapter 3.3.5.2 --- Haplotype analysis --- p.146 / Chapter 3.3.6 --- AKR1C4 --- p.147 / Chapter 3.3.6.1 --- AKR1C4 polymorphisms and risk of HCC --- p.147 / Chapter 3.3.6.2 --- Haplotype analysis --- p.148 / Chapter 3.3.7 --- AKR1D1 --- p.149 / Chapter 3.3.7.1 --- AKR1D1 polymorphisms and risk of HCC --- p.149 / Chapter 3.3.7.2 --- Haplotype analysis --- p.150 / Chapter 3.3.8 --- AKR1C3 --- p.151 / Chapter 3.3.8.1 --- AKR1C3 polymorphisms and risk of HCC --- p.151 / Chapter 3.3.8.2 --- Haplotype analysis --- p.152 / Chapter 3.3.9 --- mRNA expression study of the 5 α -reductase isoforms --- p.153 / Chapter 3.3.9.1 --- Expression of SRD5A1 and SRD5A2 mRNAin HCC patients --- p.153 / Chapter 3.3.9.2 --- Expression of SRD5A1 and SRD5A2 mRNAin prostate and HCC cell lines --- p.154 / Chapter 3.3.10 --- Overall association of polymorphisms in sex steroid metabolism genes and risk of HCC --- p.154 / Chapter 3.3.11 --- GMDR analysis --- p.156 / Chapter 3.4 --- Discussion --- p.159 / Chapter 3.4.1 --- 5 α-reductase and risk of HCC --- p.159 / Chapter 3.4.1.1 --- SRD5A2 --- p.160 / Chapter 3.4.1.2 --- SRD5A1 --- p.161 / Chapter 3.4.2 --- Other genes and association with HCC --- p.162 / Chapter 3.4.2.1 --- HSD17B2 and risk of HCC --- p.162 / Chapter 3.4.2.2 --- "HSD3B1, AKR1C3, AKR1C4, AKR1D1 and risk of HCC" --- p.163 / Chapter 3.4.2.3 --- CYP19A1 and risk of HCC --- p.164 / Chapter 3.4.3 --- Gene-Gene interactions associated with HCC --- p.165 / Chapter CHAPTER 4 --- CONCLUSIONS AND PROSPECT FOR FUTURE WORK --- p.166 / Chapter 4.1 --- Conclusion --- p.166 / Chapter 4.2 --- Future works and prospect --- p.169 / REFERENCES --- p.170

Dissertation (Ph.D.)--University of South Florida, 2007. / Title from PDF of title page. Document formatted into pages; contains 155 pages. Includes vita. Includes bibliographical references.