Thesis (M.P.H.)--University of Sydney, 2001. / Includes tables. Title from title screen (viewed Apr. 23, 2008). Submitted in fulfilment of the requirements for the degree of Master of Public Health to the Dept. of Public Health and Community Medicine, Faculty of Medicine. Includes bibliography. Also available in print form.

Purpose Primary Open Angle Glaucoma (POAG) is an important cause of irreversible visual loss in South Africa. POAG is asymptomatic, yet early detection and treatment can prevent visual loss. POAG has a genetic component, and identifying genetic risk factors could facilitate early detection as well as elucidate pathogenic mechanisms of the disease. POAG is more common in populations of African descent, but has been understudied in the context of POAG genetic risk factors in these populations. The purpose of this research was to identify genetic risk factors for POAG in black South Africans. Methods Self-identified black South African POAG patients and unaffected control participants were enrolled at St John Eye Hospital in Soweto. The study population was evaluated in case-control association studies for genetic risk factors in the following genomic regions: CDKN2B/CDKN2BAS-1, MYOC, TMCO1, CAV1/CAV2, CYP1B1, WDR36, COL1A1, COL1A2, COL5A1, COL8A2, ZNF469, SIX1/SIX6, ATOH7 and the chromosome 2p16 locus. The study was powered to detect moderate-sized genetic effects. Family members of participants identified with potentially pathogenic mutations in MYOC were counselled, screened for the mutations and clinically screened for glaucoma. Genotyping data from SNPs in TMCO1, CAV1/CAV2, CDKN2BAS-1 and SIX1/SIX6 that had also been genotyped in a West African and an African American population were compared with the South African data and the three datasets were combined to create a larger sample of individuals of African descent for association analyses. Results There were 247 POAG patients and 255 control participants enrolled in the study that were representative of the black population of South Africa. The POAG participants had advanced disease with more than half having severe visual impairment from the disease. Potentially pathogenic mutations in MYOC were identified in 4.2% of the POAG patients (Lys500Arg in 1.2%, Gly374Val in 0.9% and Tyr453del in 2.3%) and in 20% of the family members screened. The screening successfully identified individuals at high risk for future visual loss and enabled them to receive counselling and follow-up. Lys500Arg is a benign variant, whereas Gly374Val and Tyr453del are pathogenic. Tyr453del is incompletely penetrant. In the association studies, single SNPs in the COL1A1, ZNF469 and MYOC regions showed marginal associations with POAG, but the identified associations did not withstand correction for multiple testing. Ocular quantitative trait association analyses also yielded no significant associations after correction but a significant association was identified with type 2 diabetes mellitus and rs12522383 in WDR36. There was also a significant association identified with SNP rs10120688 in CDKN2BAS-1 and visual impairment in the African American dataset. Combining the three datasets of individuals of African descent increased the power to detect small genetic effects and identified suggestive associations with SNPs in TMCO1 and CAV1/CAV2. Conclusions Black South Africans with POAG may have a MYOC mutation that either causes or contributes to their risk for developing POAG in approximately 3.3%. MYOC mutation screening in affected families successfully demonstrated the value of genetic information in identifying and protecting individuals at risk for visual loss from glaucoma. The genetic risk associated with the candidate genes evaluated in this study and POAG in black South Africans, if such a risk exists, is a small risk. There is therefore a critical need for further genetic association studies in POAG in this significantly affected population to identify other genetic risk factors. This study has important implications for the management and counselling of black South African patients with POAG and their families.

No description available.

Fan Baojian. / "June 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 101-126). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Leung Yuk Fai. / "June 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 132-166). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Dexamethasone (DEX) and triamcinolone acetonide (TA) are widely used in clinical practice for ocular anti-inflammation. The most common side effect of these two corticosteroids is the rise of intraocular pressure that leads to death of the retinal ganglion cells, a feature of POAG. We investigated the differential gene expression profiles induced by DEX and TA treatment in human trabecular meshwork (hTM) cells using microarray technology. A number of genes differentially expressed in hTM cells were identified under DEX and TA treatment, mainly involving in proteolysis, cell adhesion and acute phase response. Five genes (MYOC, GAS1, SENP1, ZNF343 and SOX30) were commonly differentially expressed in both DEX and TA treatment. It indicates that DEX and TA may share similar effect on hTM cells, which may associate with the onset of ocular hypertension. / In one Chinese juvenile onset POAG (JOAG) family with autosomal dominant inheritance, a novel locus at 15822-q24 (GLC1N) was identified using genome-wide scan, supported by clinical, linkage, and haplotype transmission data. The critical region covered a genetic distance of 16.6 Mb. To search for disease genes within this new JOAG locus, we screened NR2E3, SMAD6 and CLN6 for mutations. However, no mutations was found in the family members. We attempted a new gene-based SNPs genotyping approach to search for susceptibility genes to JOAG in this novel locus by using 97 unrelated JOAG patients and 99 unrelated control subjects. Significant association was identified in a set of 6 adjacent SNPs out of 122 gene-based SNPs. Among them, one non-synonymous SNP rs3743171 in the SLC24A1 gene was incompletely segregated in the JOAG family. Our findings indicate the mutation in other regions of SLC24A1 may be responsible for JOAG in this family, or another gene in this region may be the actual cause of glaucoma. / Primary open angle glaucoma (POAG) is a leading cause of visual impairment and blindness worldwide. Genetic factors play a major role in the etiology of POAG. This thesis describes our investigations of the POAG causative genes using genome-wide DNA scanning by linkage/association analysis and RNA level scanning by microarray technology. / Wang Danyi. / "September 2006." / Adviser: Calvin Chi Pui Pang. / Source: Dissertation Abstracts International, Volume: 68-08, Section: B, page: 5155. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 139-181). / 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. / Abstracts in English and Chinese. / School code: 1307.

Thesis (M.P.H.)--University of Alabama at Birmingham, 2009. / Title from first page of PDF file (viewed on June 11, 2009). Includes bibliographical references (p. 36-40).

Thesis (Ph. D.)--University of California, San Diego, 1999. / Vita. Includes bibliographical references (leaves 139-141).

Apart from associated genes, a candidate causative gene NTF4 was screened and two novel putative mutations (Gly157Ala and Ala182Val) detected, likely accounting for 0.29% of POAG. In the exploration of new POAG genes, two functional candidates CNTF and SPARC were screened and excluded. / Differential association profiles were found for SNPs in/near CAV1, CAV2, CYP46A1, LMX1B, PLXDC2, TLR4, TMTC2, ZP4 and 2p16.3. SNPs at CAV1, CAV2, TLR4 and 2p16.3 were associated with POAG, whilst SNPs around other genes were unlikely to be risk factors for the disease, at least in Chinese. TLR4 rs7037117 was associated with HTG in southern Chinese (P=0.0016, OR=2.72, recessive model). SNP rs1533428 at 2p16.3 showed an age-specific association of with late-onset POAG (age at diagnosis >60 years; P=1.14x10-5, OR=2.02, dominant model) but not with juvenile- and adult-onset POAG. Moreover, rs1533428 formed a joint effect with rs7037117 to confer stronger risk to HTG (P=2.8x10 -4, OR=4.53). Besides, rs4236601 near the CAV1 and CAV2 genes was confirmed as a risk factor for POAG and another two protective SNPs rs6975771 and rs959173 were identified; moreover, that the risk and protective alleles were located in different haplotypes suggested multiple roles of the genes. / Glaucoma is a group of degenerative optic neuropathies and the leading cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG) is a major type of glaucoma in most populations. It is classified into high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) according to the level of intraocular pressure. POAG has complex etiology. It could be monogenic or caused by multiple risk factors. At least 22 linkage loci have been mapped, with 3 genes (MYOC, OPTN, and WDR36 ) identified. Also, more than 30 susceptibility genes have been reported, many of which, however, remain unverified. / In the mapping of the causal gene at GLC1N, a truncation mutation c.1090delT in the MEGF11 gene was found to be cosegregated with glaucoma in the GLC1N-linked pedigree. Subsequent identification of c.1090delT in an unrelated JOAG patient supported that it is a disease-causing mutation. The identification of four splice-site mutations (IVS17+2insT, IVS17-4C>G, IVS17-2A>G and c.2472A>C) exclusively in patients provided further evidence supporting MEGF11 as a causative gene for POAG. Mutations in this gene likely account for approximately 1% of POAG or 2% of JOAG. / This thesis describes our work on the identification of new POAG genes by using a 3-tiered strategy: (1) to identify new genetic profiles of variants around the CAV1, CAV2, CYP46A1, LMX1B, NTF4, PLXDC2, TLR4, TMTC2, ZP4 genes and the 2p16.3 locus; (2) to evaluate CNTF and SPARC as disease genes for POAG; and (3) to map the causal gene at the GLC1N locus for juvenile-onset POAG (JOAG). / Totally 1645 unrelated participants were enrolled, including a Hong Kong cohort of 281 HTG, 311 NTG and 248 controls, a Shantou cohort of 102 HTG, 28 NTG and 298 controls and, a Beijing cohort of 177 HTG and 200 controls. Also involved were members of the GLC1M-linked Philippine pedigree and the GLC1N-linked Hong Kong pedigree with JOAG, which have been previously described. / Chen, Lijia. / Adviser: Chi Pui Pang. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 185-210). / 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.

OBJETIVO: avaliar a reprodutibilidade dos picos de pressão intraocular e a flutuação obtidas durante o teste de sobrecarga hídrica em pacientes glaucomatosos tratados com um longo intervalo de seguimento. MÉTODOS: análise retrospectiva de 34 pacientes portadores de glaucoma primário de ângulo aberto, sob tratamento clínico, atendidos durante o período de uma semana no ambulatório de um dos investigadores (RSJ). Os pacientes foram submetidos ao teste de sobrecarga hídrica, realizado em duas visitas consecutivas, sem alteração do regime terapêutico. O intervalo médio entre os testes foi de 4,85 (intervalo, 3-6) meses. A reprodutibilidade do pico e a flutuação durante o teste de sobrecarga hídrica foram avaliadas utilizando coeficientes de correlação intraclasse. A análise de Bland-Altman foi utilizada para avaliar a concordância entre os picos de pressão intraocular e a flutuação, medidos entre dois testes consecutivos. RESULTADOS: trinta e quatro olhos de 34 pacientes foram estudados. Não houve diferenças significativas nos valores de pressão intraocular basal (média ± desvio-padrão, 11,73 ± 2,36 e 11,61 ± 2,71 mmHg; p = 0,72) e picos (14,55 ± 3,41 e 15,02 ± 3,66 mmHg, respectivamente; p = 0,163) detectados durante o teste de sobrecarga hídrica entre a primeira e a segunda visitas. Também não houve diferença significativa entre os valores médios de flutuação da pressão intraocular (2,82 ± 1,99 e 3,41 ± 2,54 mmHg, respectivamente; p = 0,135). Os picos de pressão intraocular e a flutuação apresentaram coeficientes de correlação intraclasse de 0,85 (p < 0,001) e 0,50 (p < 0,001), respectivamente. CONCLUSÕES: neste estudo, os resultados demonstraram excelente reprodutibilidade dos picos de pressão intraocular durante o teste de sobrecarga hídrica. Entretanto, a flutuação da pressão intraocular não revelou boa reprodutibilidade / OBJECTIVE: To evaluate the reproducibility of intraocular pressure peaks and fluctuation elicited during the water drinking test in treated glaucomatous patients with a long follow-up interval. METHODS: 34 treated primary openangle glaucoma patients evaluated in retrospective cohort study in a tertiary care practice. All patients underwent the water drinking test performed in two consecutive visits without any change in the therapeutic regimen. The mean interval between tests was 4.85 (range, 3-6) months. Reproducibility of peak and fluctuation during the water drinking test was assessed using intraclass correlation coefficients. Bland-Altman analysis was used to assess the agreement of intraocular pressure peaks and fluctuation measured between two consecutive tests. RESULTS: There were no significant differences in baseline intraocular pressure values (mean ± standard deviation, 11.73 + 2.36 and 11.61+2.71 mmHg; p=0.72) and peaks (14.55+3.41 and 15.02 ± 3.66 mmHg, respectively; p=0.163) detected during the water drinking test between the first and second visits. There was also no significant difference between the average intraocular pressure fluctuation values (2.82 ± 1.99 and 3.41 ± 2.54 mmHg, respectively; p=0.135). Intraocular pressure peaks and fluctuation presented intraclass correlation coefficients of 0.85 (p < 0.001) and 0.50 (p < 0.001), respectively. CONCLUSIONS: Our results demonstrate excellent reproducibility of intraocular pressure peaks during the water drinking test. Intraocular pressure fluctuation did not reveal good reproducibility, though