Hepcidin-25, ein 2000 entdecktes Peptidhormon, das eine Schlüsselrolle im Eisenstoffwechsel spielt, hat das Verständnis von Eisenerkrankungen revolutioniert. In dieser Studie wurde LC gekoppelt mit einem Triple-Quadrupol MS in einer schnellen und robusten Methode zur Quantifizierung von Hepcidin-25 in menschlichem Serum verwendet, welche letztlich in Routine-Laboratorien genutzt werden soll. Zu diesem Zweck wurden zwei Probenvorbereitungsstrategien und zwei komplementäre LC Bedingungen untersucht, wobei eine saure mobile Phase (0,1% TFA) mit einem neuartigen Ansatz unter der Verwendung einer basischen mobilen Phase (0,1% NH3) verglichen wurde. In einem laborinternen Vergleich beider LC-MS/MS Methoden wurde Hepcidin-25 in humanen Proben unter Verwendung der gleichen Kalibrierstandards quantifiziert und eine sehr gute Korrelation der Ergebnisse ermittelt. Hierbei wurde die Analysestrategie mit saurer mobiler Phase als hochsensitiv (LOQ von 0,5 μg/L) und präzise (CV <15%) befunden und als Kandidat einer Referenzmethoden für die Hepcidin-25 Quantifizierung in realen Proben empfohlen. Einer der neuartigen Aspekte der Methodik war die Verwendung von Amino- und Fluor-silanisierten Autosampler-Fläschchen, um die Adsorption des 25 Reste umfassenden Peptids anOberflächen zu reduzieren. Darüber hinaus wurde diese LC-MS/MS-Methode in einer internationalen Ringversuchsstudie eingesetzt, bei der ein sekundäres Referenzmaterial als Kalibrierstandard verwendet wurde, und gemäß des International Consortium for Harmonization of Clinical Laboratory Results (ICHCLR) als optimal bewertet. In dieser Arbeit wurde die Bildung von Hepcidin-Komplexen mit Kupfer(II) untersucht. Die erste Umkehrphasen-chromatographische Trennung von Hepcidin-25/Cu(II) und Hepcidin-25 (Kupfer "frei") wurde unter Verwendung von mobilen Phasen mit 0,1% NH3 erreicht. LC-MS/MS und FTICR-MS wurden für die Charakterisierung der gebildeten Hepcidin-25-Cu(II)-Spezies bei pH-Werten von 11 bzw. 7,4 verwendet. / Hepcidin-25, a key iron-regulatory peptide hormone discovered in 2000, has revolutionized the understanding of iron-related pathology. This study applied LC-MS/MS, using the triple quadrupole mass spectrometer, in a rapid and robust analytical strategy for the quantification of hepcidin-25 in human serum, to be implemented in routine laboratories. For this purpose, two sample preparation strategies and two complementary LC conditions were investigated, where the use of acidic mobile phases (0.1% TFA) was compared with a novel approach involving solvents at high pH (0.1% NH3). The application of these LC-MS/MS methods to human samples in an intra-laboratory comparison, using the same hepcidin-25 calibrators, yielded a very good correlation of the results. The LC-MS/MS employing trifluoroacetic acid-based mobile phases was selected as a highly sensitive (LOQ of 0.5 µg/L) and precise (CV<15%) method and was recommended as a reference method candidate for hepcidin-25 quantification in real samples. One of the novel aspects of the methodology was the use of amino- and fluoro-silanized autosampler vials to reduce the interaction of the 25-residue peptide to laboratory glassware surfaces. Moreover, this LC-MS/MS method was used for an international round robin study, applying a secondary reference material as a calibrator and its performance was found to be in the optimal range as defined by the International Consortium for Harmonization of Clinical Laboratory Results (ICHCLR). In this work, the formation of hepcidin-25 complexes with copper(II) was investigated. The first reversed-phase chromatographic separation of hepcidin-25/Cu2+ and hepcidin-25 (copper “free”) was achieved by applying mobile phases containing 0.1% NH3. LC-MS/MS and FTICR-MS were applied for the characterization of the formed hepcidin-25-Cu(II) species at pH values of 11 and 7.4 respectively. A new species corresponding to hepcidin-25 complexed with two copper ions was identified at high pH.

Obwohl die Struktur und das Ausmaß dendritischer Verzweigungen eine wichtige Rolle bei der Informationsübertragung neuronaler Zellen spielen, ist bislang wenig über die Bausteine und Molekularmechanismen des Dendritenwachstums bekannt. Unter der Verwendung primär dissoziierter hippocampaler Zellkulturen embryonaler Mäuse untersuchte ich frühe Stadien des Zellfortsatzwachstums. Dabei konnte ich SNAP-25 (synaptosomal associated protein of 25 kDA), ein Schlüsselprotein der regulierten Exozytose, nicht nur in Axonen und terminalen Axonendigungen, sondern auch anhand von Doppelimmunmarkierungen mit den dendritischen Markern Transferrin-Rezeptor und MAP-2 in Dendriten lokalisieren. Die spezifische Inaktivierung von SNAP-25 durch Botulinumneurotoxin A (BoNT/A) führte zur Hemmung des Axonwachstums und des Vesikelrecyclings in terminalen Axonendigungen. Darüberhinaus wurde auch das Wachstum dendritischer Fortsätze von Körner- und Pyramidenzellen durch BoNT/A signifikant gehemmt. Daraus läßt sich schließen, daß SNAP-25, im Gegensatz zu Synaptobrevin, an konstitutiven Prozessen in den Axonen und Dendriten hippocampaler Neurone beteiligt ist. / Structure and dimension of the dendritic arbor are important determinants of information processing by the nerve cell, but mechanisms and molecules involved in dendritic growth are essentially unknown. I investigated early mechanisms of dendritic growth using mouse fetal hippocampal neurons in primary culture, which form processes during the first week in vitro. I detected a key component of regulated exocytosis, SNAP-25 (synaptosomal associated protein of 25 kDa)., in axons and axonal terminals as well as in dendrites identified by the occurrence of the dendritic markers transferrin receptor and MAP2. Selective inactivation of SNAP-25 by botulinum neurotoxin A (BoNTA) resulted in inhibition of axonal growth and of vesicle recycling in axonal terminals. In addition, dendritic growth of hippocampal pyramidal and granule neurons was significantly inhibited by BoNTA. These observations indicate that SNAP-25, but not synaptobrevin, is involved in constitutive axonal growth and dendrite formation by hippocampal neurons.

Le présent mémoire s’intéresse aux possibilités de sens que les textes évangéliques offrent au lecteur contemporain. En utilisant la méthode de Greimas, telle que reprise par Courtés et Delorme, le but de l’étude est principalement d’identifier les structures narratives et discursives de Luc 10, 25-3 7 afin de montrer comment ce texte, abordé comme un tout de signification, informe la lecture. L’analyse de ce dialogue mettra en lumière le fait que Jésus invite le légiste à transformer la façon qu’il a de concevoir la finalité du savoir dans sa propre vie. La description sémiotique nous permettra de constater que le changement de perspective qu’il est invité à réaliser se situe au niveau de son "vouloir": c’est pourquoi nous dirons qu’il est invité à réaliser une "conversion du vouloir".

Background In South Africa, as in many other developing countries, obesity has become a major health problem causing an increase in the incidence and prevalence of various non-communicable diseases. Research has shown that excess adiposity is associated with low vitamin D status and detrimental to bone health. Low vitamin D status has been linked to various non-communicable diseases which includes osteoporosis, and also the metabolic syndrome. Information is scarce on the role of lean mass and fat mass on bone health in the black South African population. There is also a shortage of data on the association between vitamin D status and the metabolic syndrome in the South African population. Aim The main aim of this study was to examine factors (vitamin D status, socio-economic status [SES] and lifestyle risk factors) associated with body composition, including bone health, as well as predictors of change in body composition in African adults in the North West Province of South Africa. Methods The first study that forms part of this thesis was a longitudinal study aimed at examining the effects of urbanization, socio-economic status and lifestyle factors on changes in body composition over 5 years in rural and urban black South African adults. A total of 1058 men and women above age 30 years from the Prospective Urban Rural Epidemiology study were included in this study. The second study to form part of this thesis aimed to examine the association between body composition and bone health in urban black South African women. Structured questionnaires were used to collect socio-demographic and lifestyle information including medication and tobacco use. This second study is cross-sectional in design and it included 189 postmenopausal women aged > 43 years old. Dual X-ray absorptiometry was used to assess bone mineral density, lean mass and fat mass, while structured and specific questionnaires were used to assess the habitual physical activity, food frequency and fracture risk. Habitual activity energy expenditure was also measured using an accelerometer with a combined heart rate monitor. The third study aimed to examine the association of serum 25 hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) concentration, respectively, with the metabolic syndrome while controlling for adiposity in black women in the North West Province, South Africa. This third study is also cross-sectional in design and it included 209 HIV-negative urban women. Dual X-ray absorptiometry was used to assess adiposity, while habitual physical activity was accessed with questionnaire and habitual activity energy expenditure was also measured using an accelerometer with a combined heart rate monitor. Results Study 1: Over a 5-year period, body mass index (BMI) and waist circumference increased in both genders, but the change was significant for BMI (P<0.01) and waist circumference (P<0.001) in women only, indicating an increase in adiposity over time. Urban residency positively predicted changes in waist circumference in men (p < 0.05) and women (p < 0.001) as well as change in triceps skinfold thickness of men (p < 0.05). Being married positively predicted changes in BMI (p < 0.001) and waist circumference (p < 0.001) in men, while age negatively predicted changes in triceps skinfold thickness in women (p < 0.001). Study 2: Fat mass and lean mass were significantly positively associated with bone mineral density (BMD) and fracture risk when adjusted for potential confounders. However, lean mass and not fat mass remained significantly associated with femoral neck BMD (β = 0.49, p <0.001), spine BMD (β = 0.48, p< 0.0001) and hip BMD (β = 0.59, p< 0.0001). Lean mass was also negatively associated with fracture risk (β = -0.19 p =0.04) when both lean and fat mass were in the same model. Study 3: After adjusting for age, body fat, habitual physical activity, tobacco use and season, neither 25(OH)D nor PTH concentrations showed significant associations with having the metabolic syndrome. However, when body fat was replaced with waist circumference there was a weak positive association between 25(OH)D concentration and the metabolic syndrome. No significant association was found between PTH:25(OH)D ratio and the metabolic syndrome. Conclusion This thesis has highlighted that the prevalence of obesity among black South Africans is high particularly among women and urbanization played a significant role in the increasing adiposity of black South Africans in the North West province. Lean mass had a stronger association with bone health in comparison to fat mass in urban black South African women. Low 25(OH)D concentration was not associated with the metabolic syndrome while there was no significant association between PTH and the metabolic syndrome in our black South African women. / PhD (Dietetics), North-West University, Potchefstroom Campus, 2015

Background In South Africa, as in many other developing countries, obesity has become a major health problem causing an increase in the incidence and prevalence of various non-communicable diseases. Research has shown that excess adiposity is associated with low vitamin D status and detrimental to bone health. Low vitamin D status has been linked to various non-communicable diseases which includes osteoporosis, and also the metabolic syndrome. Information is scarce on the role of lean mass and fat mass on bone health in the black South African population. There is also a shortage of data on the association between vitamin D status and the metabolic syndrome in the South African population. Aim The main aim of this study was to examine factors (vitamin D status, socio-economic status [SES] and lifestyle risk factors) associated with body composition, including bone health, as well as predictors of change in body composition in African adults in the North West Province of South Africa. Methods The first study that forms part of this thesis was a longitudinal study aimed at examining the effects of urbanization, socio-economic status and lifestyle factors on changes in body composition over 5 years in rural and urban black South African adults. A total of 1058 men and women above age 30 years from the Prospective Urban Rural Epidemiology study were included in this study. The second study to form part of this thesis aimed to examine the association between body composition and bone health in urban black South African women. Structured questionnaires were used to collect socio-demographic and lifestyle information including medication and tobacco use. This second study is cross-sectional in design and it included 189 postmenopausal women aged > 43 years old. Dual X-ray absorptiometry was used to assess bone mineral density, lean mass and fat mass, while structured and specific questionnaires were used to assess the habitual physical activity, food frequency and fracture risk. Habitual activity energy expenditure was also measured using an accelerometer with a combined heart rate monitor. The third study aimed to examine the association of serum 25 hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) concentration, respectively, with the metabolic syndrome while controlling for adiposity in black women in the North West Province, South Africa. This third study is also cross-sectional in design and it included 209 HIV-negative urban women. Dual X-ray absorptiometry was used to assess adiposity, while habitual physical activity was accessed with questionnaire and habitual activity energy expenditure was also measured using an accelerometer with a combined heart rate monitor. Results Study 1: Over a 5-year period, body mass index (BMI) and waist circumference increased in both genders, but the change was significant for BMI (P<0.01) and waist circumference (P<0.001) in women only, indicating an increase in adiposity over time. Urban residency positively predicted changes in waist circumference in men (p < 0.05) and women (p < 0.001) as well as change in triceps skinfold thickness of men (p < 0.05). Being married positively predicted changes in BMI (p < 0.001) and waist circumference (p < 0.001) in men, while age negatively predicted changes in triceps skinfold thickness in women (p < 0.001). Study 2: Fat mass and lean mass were significantly positively associated with bone mineral density (BMD) and fracture risk when adjusted for potential confounders. However, lean mass and not fat mass remained significantly associated with femoral neck BMD (β = 0.49, p <0.001), spine BMD (β = 0.48, p< 0.0001) and hip BMD (β = 0.59, p< 0.0001). Lean mass was also negatively associated with fracture risk (β = -0.19 p =0.04) when both lean and fat mass were in the same model. Study 3: After adjusting for age, body fat, habitual physical activity, tobacco use and season, neither 25(OH)D nor PTH concentrations showed significant associations with having the metabolic syndrome. However, when body fat was replaced with waist circumference there was a weak positive association between 25(OH)D concentration and the metabolic syndrome. No significant association was found between PTH:25(OH)D ratio and the metabolic syndrome. Conclusion This thesis has highlighted that the prevalence of obesity among black South Africans is high particularly among women and urbanization played a significant role in the increasing adiposity of black South Africans in the North West province. Lean mass had a stronger association with bone health in comparison to fat mass in urban black South African women. Low 25(OH)D concentration was not associated with the metabolic syndrome while there was no significant association between PTH and the metabolic syndrome in our black South African women. / PhD (Dietetics), North-West University, Potchefstroom Campus, 2015

Vitamin D is an essential nutrient in the human diet. A unique property of vitamin D is that it can be produced by endogenous synthesis in the skin following sufficient Ultraviolet B (UVB) radiation. In fact, our understanding of this compound has changed, such that it is no longer consider a true vitamin, but rather a steroid hormone. De-identified data for this analysis were derived from women residing in Jeddah, Saudi Arabia who completed routine medical visits in the summer of 2009 at King Fahad Hospital (KFH). In Chapter 1,“THE ASSOCIATION BETWEEN VITAMIN D STATUS IN NORMAL WEIGHT VERSUS OBESE WOMEN RESIDING IN WESTERN SAUDI ARABIA” we evaluate the relationship between body size and serum 25(OH)D concentrations including the association between change in body size during adulthood and vitamin D status. This study examines whether the current weight and weight change since age 18 years are associated with vitamin D status. This study found that neither current weight nor adult weight gain were associated with vitamin D status in Saudi Arabian women. In chapter 2,“IS AVOIDING SUN EXPOSURE VIA SUN PROTECTION PRACTICES ASSOCIATED WITH LOW VITAMIN D STATUS IN SAUDI ARABIAN WOMEN?” we investigate whether women who avoid UV exposure have lower 25(OH)D concentrations than women who do not avoid exposure. UV exposure was defined by time in outdoor activities, use of protective clothing and sunscreen. This study demonstrated that avoiding UV exposure via indoor activity and the use of sunscreen or/and wearing protective clothing was not associated with vitamin D status. Chapter 3, “VITAMIN D STATUS AND BREAST CANCER IN SAUDI ARABIAN WOMEN: A CASE CONTROL STUDY” we examine if vitamin D status as assessed by serum concentrations of 25(OH)D would be lower in breast cancer cases as compared to controls. This study demonstrated that there is a significant relationship between higher serum concentrations of 25(OH)D and lower risk of breast cancer. Chapter 4, “IMPLICATIONS AND FUTURE DIRECTIONS” is presented a summary of key findings from the three studies in this dissertation to determine avenues of further research. The appendices consist of materials related to the dissertation work.

In this diploma thesis, capillary columns with an inner diameter of 530 microns filled with gel particles were prepared. These columns are intended for gel chromatography. Three various methods of filling were used for their preparation. The first method was based on filling of wet particles in suspension with the organic solvent, followed by drying and swelling of particles with water into the form of gel. The second method used filling of wet particles in the suspension form with the aqueous phase. The last method started with suction of dry gel particles by air and continued with their subsequent swelling with water into the form of the gel. The prepared columns have been compared analysing hyaluronic acid and thiourea. The basic parameters specified for the gel column chromatography were determined by using phenylalanine. The pressure characteristics depending on the flow rate of mobile phase were used to compare the quality of packing of the columns prepared by various methods.

Introduktion: Systemisk Lupus Erythematosus är en prototypisk autoimmun sjukdom som gör att immunförsvarets antikroppar angriper kroppens egna vävnader, vilket leder till kronisk inflammation i kroppens organsystem. Idag finns ingen verksam behandling för Systemisk Lupus Erythematosus. Syftet med denna studie var att undersöka hur Dvitamintillskott påverkar Systemisk Lupus Erythematosus. Metod: Artiklarna hittades i databasen ”Pubmed” med sökningen ”Systemic Lupus Erythematosus and vitamin D supplementation”. Bland sökresultaten fanns sex relevanta artiklar som hade undersökt effekten av D-vitamintillskott på SLE. Resultat: Mer än hälften av patienterna i samtliga studier nådde serum 25(OH) D-nivåer som ansågs vara tillräckliga. D-vitamintillskottet minskade Th1/Th17-cellerna men ökade också Treg-celler och Th2-celler. Tre studier visade sig ha en signifikant minskning i sjukdomsaktivitet och anti-dsDNA antikroppar. Komplement C3 minskade i studie 2. Diskussion: Fem av studierna tyder på att oral administrering av D-vitamin tillskott har gett positiv inverkan på SLE. Två av de granskade studierna rapporterades inge positiv klinisk effekt hos deltagarna. Slutsats: D-vitamintillskott dämpar immunsystemet genom att öka Treg-celler och Th-2-celler men även minska Th1/Th17-celler och B-celler samt produktionen av autoantikroppar och anti-dsDNA-antikroppar. Effekten av D-vitamintillskott på komplement C3 och C4 är oklar. Det krävs dock fler studier med fler deltagarantal för att dra en slutsats om Dvitamintillskott kan användas som behandling för SLE. / Background: Systemic Lupus Erythematosus is a prototypical autoimmune disease in which antibodies attack healthy tissues in the body, causing inflammation in several organs. Aim: The aim of this literature study was to investigate the effect of Vitamin Dsupplementation on SLE. Method: The articles were searched in the database called ”Pubmed” using the search terms ”Systemic Lupus Erythematosus and Vitamin D supplementation”. Six of the articles which examined the effects of D-vitamin supplementation on SLE were relevant for this study. Result: More than half of the patients in all six studies reached sufficient serum 25(OH)D. Vitamin D-supplement reduced Th1/Th17-cells but increased Tregs-cells and Th2-cells. 3 studies showed a decrease in disease-activity and anti-dsDNA. C3 decreased in study 2. Discussion: Five studies indicated that the oral administration of vitamin-D supplementation had a positive effect on SLE. Two of the examined studies did not observe any clinical effect of the vitamin-D supplement. Conclusion: Vitamin-D supplement suppresses the immunesystem by increasing Treg cells and Th-2 cells but also reducing Th1/Th17-cells and B-cells as well as the production of autoantibodies and anti-dsDNA antibodies. The effect of vitamin D-supplement is unclear. More studies with more participants are required to determine if vitamin-D supplement can be used as a treatment for SLE.

Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-06-30T17:55:06Z No. of bitstreams: 1 TES_CAMILA_GARCIA_KIELING_COMPLETO.pdf: 2798917 bytes, checksum: 9bb0d9ac61c8fb787fe5c6f6e4d11443 (MD5) / Made available in DSpace on 2017-06-30T17:55:06Z (GMT). No. of bitstreams: 1 TES_CAMILA_GARCIA_KIELING_COMPLETO.pdf: 2798917 bytes, checksum: 9bb0d9ac61c8fb787fe5c6f6e4d11443 (MD5) Previous issue date: 2017-03-30 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / This thesis presents an analysis of newspapers narratives representing Brazilian and Portuguese hegemonic presses in two moments of institutional breakdowns: the civil-military coup of 1964 in Brazil and the revolution of April 25, 1974 in Portugal. In the first case, the result was the overthrow of President Jo?o Goulart and the beginning of a military dictatorship that lasted 21 years; in the second, the fall of an autocratic regime that existed for 48 years and the beginning of a revolutionary process that consolidated the country democracy. The research corpus is O Estado de S. Paulo and Jornal do Brasil in Brazil and Di?rio de Not?cias and Rep?blica in Portugal. In our approach institutional breakdowns are events that give access ? through media narratives ? to historical consciousness for they express particular modes of grasping changes regarding the mass media centrality in the modern conception of an event, according to Nora (1979). Through the narratives of the lived and the imaginary (SILVA, 2006; 2010) we seek to unveil the object of our research through theoretical-methodological covering. Therefore we reflected upon the event category, having Nora (1979) and Sodr? (2009) as the major references. With the comparative method of Detienne (2004), our analysis approach was oriented by the Critical Narrative Analysis focused on journalism, as proposed by Motta (2013) Understanding the journalistic narrative as a product of the technology of the imaginary (SILVA, 2006) through which facts are challenged through its spectacularisation, our analysis has been conducted by comparable categories that enabled us to acquire an understanding of the imaginary dimension of the journalistic narratives used to report those episodes of institutional rupture, namely: the composition of intrigue, the characters, the media repercussions, the lexicon and the expressions of time. / Nossa tese apresenta uma an?lise das narrativas de jornais representativos das imprensas hegem?nicas brasileira e portuguesa em dois momentos de ruptura institucional: o Golpe Civil-Militar de 1964 no Brasil e a Revolu??o de 25 de Abril de 1974 em Portugal. No primeiro caso, ocorre a derrubada do presidente Jo?o Goulart e o in?cio de uma ditadura militar que durou 21 anos. No segundo, a queda de um regime autocr?tico que j? se prolongava por 48 anos e o come?o de um processo revolucion?rio que consolidou a democracia naquele pa?s. Constituem o nosso corpus de pesquisa, no Brasil, O Estado de S. Paulo e Jornal do Brasil e, em Portugal, Di?rio de Not?cias e Rep?blica. Em nossa abordagem, as rupturas institucionais s?o eventos que d?o acesso ? atrav?s das narrativas midi?ticas ? ? consci?ncia hist?rica, porque expressam modos particulares de apreens?o da mudan?a, tendo em vista a centralidade dos meios de comunica??o na concep??o contempor?nea de acontecimento, conforme observado por Nora (1979). Atrav?s do percurso das narrativas do vivido e do imagin?rio (SILVA, 2006; 2010) buscamos o desvelamento de nosso objeto de pesquisa atrav?s do recobrimento te?rico-metodol?gico. Para tanto, realizamos uma reflex?o acerca da categoria acontecimento, tendo como refer?ncias principais Nora (1979) e Sodr? (2009). Com o m?todo comparativo de Detienne (2004), nossa t?cnica de an?lise foi direcionada pela An?lise Cr?tica da Narrativa voltada ao jornalismo, tal como proposta por Motta (2013). Compreendendo a narrativa jornal?stica como produto de uma tecnologia do imagin?rio (SILVA, 2006) que interpela os fatos por meio de sua espetaculariza??o, nossa an?lise ? conduzida por categorias compar?veis, as quais nos permitiram compreender a dimens?o imagin?ria das narrativas jornal?sticas analisadas sobre os referidos epis?dios de ruptura institucional, a saber: a composi??o da intriga, as personagens, as repercuss?es midi?ticas, o l?xico e as express?es do tempo.

Submitted by FERNANDA DA SILVA VON PORSTER (fdsvporster@univates.br) on 2016-08-31T19:30:52Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) 2015NathaliaGrave.pdf: 1012668 bytes, checksum: 34206baa81b06129beaa75c62787bbc4 (MD5) / Approved for entry into archive by Ana Paula Lisboa Monteiro (monteiro@univates.br) on 2016-09-05T19:29:54Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) 2015NathaliaGrave.pdf: 1012668 bytes, checksum: 34206baa81b06129beaa75c62787bbc4 (MD5) / Made available in DSpace on 2016-09-05T19:29:54Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) 2015NathaliaGrave.pdf: 1012668 bytes, checksum: 34206baa81b06129beaa75c62787bbc4 (MD5) Previous issue date: 2016-08 / Introdução: Muitos estudos tem relacionado a deficiência de vitamina D com o risco para as doenças crônicas, principalmente obesidade e dislipidemia. A vitamina D age através da ligação ao receptor de vitamina D (VDR), o qual forma heterodímeros com o receptor do retinoide X gama (RXRG). O gene GC codifica a proteína de ligação da vitamina D (DBP), a qual é responsável pelo transporte da vitamina D na corrente sanguínea. Considerando que a genética desempenha um papel importante na etiologia destas doenças, poucos estudos analisam a associação de variantes em genes da rota da vitamina D com parâmetros antropométricos e bioquímicos relacionados a estes desfechos. Objetivo: Investigar a associação entre polimorfismos de genes relacionados à rota da vitamina D, rs2228570 (gene VDR), rs2134095 (gene RXRG), rs7041 (gene GC), e parâmetros antropométricos e bioquímicos em uma amostra de adultos. Métodos: Medidas antropométricas e bioquímicas foram avaliadas em 542 indivíduos adultos de ambos os gêneros em uma amostra de base populacional. O DNA genômico foi extraído a partir de amostra de sangue e os polimorfismos foram genotipados pela reação em cadeia da polimerase (PCR) através de discriminação alélica TaqMan (Applied Biosystems, Foster City, CA). As comparações dos desfechos entre os genótipos foram feitas usando ANOVA, Kruskal-Wallis, qui-quadrado de Pearson ou teste exato de Fisher, e as interações gene-gene foram avaliadas usando modelo linear geral. Resultados: Não identificamos nenhum efeito principal dos polimorfismos nos parâmetros avaliados. No entanto, ao analisarmos as interações gene-gene, detectamos uma interação significativa entre os genes RXRG e GC sobre os níveis de colesterol LDL. Conclusões: Nossos achados evidenciaram uma interação significativa entre polimorfismos de dois genes da rota da vitamina D, rs2134095 (RXRG) e rs7041 (GC) sobre os níveis de colesterol LDL, corroborando os achados da literatura que tem consistentemente relacionado a vitamina D com o perfil lipídico. / Introduction: Many studies have related vitamin D deficiency with the risk for chronic diseases, especially obesity and dyslipidemia. Vitamin D acts by binding to the vitamin D receptor (VDR), which form heterodimers with the retinoid X receptor gamma (RXRG). The GC gene encoding the binding protein Vitamin D (BPD), which is responsible for the vitamin D transport in the bloodstream. Considering that genetics play a significant role in the etiology of these diseases, few studies have analyzed the association of variants in genes of vitamin D route anthropometric and biochemical parameters related to these outcomes. Objective: To investigate the association between gene polymorphisms related to vitamin D route, rs2228570 (VDR gene), rs2134095 (RXRG gene), rs7041 (GC gene), and anthropometric and biochemical parameters in a sample of adults. Methods: anthropometric and biochemical measures were assessed in 542 adults of both genders in a population-based sample. Genomic DNA was extracted from blood sample and polymorphisms were genotyped by polymerase chain reaction (PCR) using the TaqMan allelic discrimination (Applied Biosystems, Foster City, CA). Comparisons of outcomes between genotypes were performed using ANOVA, Kruskal-Wallis test, chi-square test or Fisher's exact test, and gene-gene interactions were assessed using general linear model. Results: We have not identified any major effect of polymorphisms in the evaluated parameters. However, when we analyze the gene-gene interactions, we detected a significant interaction between RXRG and GC genes on LDL cholesterol levels. Conclusions: Our findings showed a significant interaction between polymorphisms in two genes of vitamin D route, rs2134095 (RXRG) and rs7041 (GC) on the levels of LDL cholesterol, corroborating literature findings that have consistently related to vitamin D with the profile lipid.