Association between TCF7L2 gene polymorphisms and susceptibility to Type 2 Diabetes Mellitus: a large Human Genome Epidemiology (HuGE) review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Transcription factor 7-like 2 (<it>TCF7L2</it>) has been shown to be associated with type 2 diabetes mellitus (T2MD) in multiple ethnic groups in the past two years, but, contradictory results were reported for Chinese and Pima Indian populations. The authors then performed a large meta-analysis of 36 studies examining the association of type 2 diabetes mellitus (T2DM) with polymorphisms in the <it>TCF7L2 </it>gene in various ethnicities, containing rs7903146 C-to-T (IVS3C>T), rs7901695 T-to-C (IVS3T>C), a rs12255372 G-to-T (IVS4G>T), and rs11196205 G-to-C (IVS4G>C) polymorphisms and to evaluate the size of gene effect and the possible genetic mode of action.</p> <p>Methods</p> <p>Literature-based searching was conducted to collect data and three methods, that is, fixed-effects, random-effects and Bayesian multivariate mete-analysis, were performed to pool the odds ratio (<it>OR</it>). Publication bias and study-between heterogeneity were also examined.</p> <p>Results</p> <p>The studies included 35,843 cases of T2DM and 39,123 controls, using mainly primary data. For T2DM and IVS3C>T polymorphism, the Bayesian <it>OR </it>for TT homozygotes and TC heterozygotes versus CC homozygote was 1.968 (95% credible interval (<it>CrI</it>): 1.790, 2.157), 1.406 (95% <it>CrI</it>: 1.341, 1.476), respectively, and the population attributable risk (PAR) for the TT/TC genotypes of this variant is 16.9% for overall. For T2DM and IVS4G>T polymorphism, TT homozygotes and TG heterozygotes versus GG homozygote was 1.885 (95%<it>CrI</it>: 1.698, 2.088), 1.360 (95% <it>CrI</it>: 1.291, 1.433), respectively. Four <it>OR</it>s among these two polymorphisms all yielded significant between-study heterogeneity (P < 0.05) and the main source of heterogeneity was ethnic differences. Data also showed significant associations between T2DM and the other two polymorphisms, but with low heterogeneity (<it>P </it>> 0.10). Pooled <it>OR</it>s fit a codominant, multiplicative genetic model for all the four polymorphisms of <it>TCF7L2 </it>gene, and this model was also confirmed in different ethnic populations when stratification of IVS3C>T and IVS4G>T polymorphisms except for Africans, where a dominant, additive genetic mode is suggested for IVS3C>T polymorphism.</p> <p>Conclusion</p> <p>This meta-analysis demonstrates that four variants of <it>TCF7L2 </it>gene are all associated with T2DM, and indicates a multiplicative genetic model for all the four polymorphisms, as well as suggests the <it>TCF7L2 </it>gene involved in near 1/5 of all T2MD. Potential gene-gene and gene-environmental interactions by which common variants in the <it>TCF7L2 </it>gene influence the risk of T2MD need further exploration.</p

Prevalência de diabetes e hipertensão no Brasil baseada em inquérito de morbidade auto-referida, Brasil, 2006 Prevalencia de diabetes e hipertensión en Brasil basado en pesquisa de morbilidad auto-referida, Brasil, 2006 Prevalence of diabetes and hypertension based on self-reported morbidity survey, Brazil, 2006

OBJETIVO: Estimar a prevalência de diabetes e de hipertensão auto-referidas e seus números absolutos no Brasil. MÉTODOS: Foram analisados dados referentes aos 54.369 indivíduos com idade >18 anos entrevistados pelo sistema de Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico (VIGITEL), realizado nas 27 capitais brasileiras em 2006, que responderam positivamente a questões sobre pressão alta e diabetes. Os percentuais de hipertensão e diabetes auto-referidas estimados na amostra foram projetados para a população brasileira segundo idade, sexo e estado nutricional, utilizando o método direto de padronização. RESULTADOS: A prevalência de diabetes foi de 5,3%, maior entre as mulheres (6,0% vs. 4,4%), variando de 2,9% em Palmas (TO) a 6,2% em São Paulo (SP). A prevalência de hipertensão foi de 21,6% (21,3;22,0), maior entre as mulheres (24,4% vs. 18,4%), variando de 15,1% em Palmas a 24,9% em Recife (PE). As prevalências aumentaram com categorias de idade e nutrição. Estimou-se haver no Brasil um total de 6.317.621 de adultos que referem ter diabetes e 25.690.145 de adultos que referem ter hipertensão. CONCLUSÕES: As prevalências de diabetes e hipertensão auto-referidas são elevadas no Brasil. O monitoramento destas e outras condições de saúde pode ser feito por estratégias como a do VIGITEL, preferencialmente se acompanhado de estudos de validação, visando a generalização de resultados.<br>OBJETIVO: Estimar la prevalencia de diabetes y de hipertensión auto-referidas y sus números absolutos en Brasil. MÉTODOS: Fueron analizados datos referentes a los 54.369 individuos con edad >18 años entrevistados por el Sistema de Vigilancia de Factores de Riesgo y Protección para Enfermedades Crónicas por Pesquisa Telefónica (VIGITEL), realizado en las 27 capitales brasileras en 2006, que respondieron positivamente a preguntas sobre presión alta y diabetes. Los porcentajes de hipertensión y diabetes auto-referidas estimados en la muestra fueron proyectados para la población brasilera según edad, sexo y estado nutricional, utilizando el método directo de estandarización. RESULTADOS: La prevalencia de diabetes fue de 5,3%, mayor entre las mujeres (6,0% vs. 4,4%), variando de 2,9% en Palmas (Norte de Brasil) a 6,2% en Sao Paulo (Sureste). La prevalencia de hipertensión fue de 21,6% (21,3;22,0), mayor entre las mujeres (24,4% vs. 18,4%), variando de 15,1% en Palmas a 24,9% en Recife (Noreste). Las prevalencias aumentaron con categorías de edad y nutrición. Se estimó haber en Brasil un total de 6.317.621 de adultos que refieren tener diabetes y 25.690.145 de adultos que refieren tener hipertensión. CONCLUSIONES: Las prevalencias de diabetes e hipertensión auto-referidas son elevadas en Brasil. El monitoreo de estas y otras condiciones de salud puede ser realizado por estrategias como la del VIGITEL, preferiblemente acompañado de estudios de validez, visando la generalización de los resultados.<br>OBJECTIVE: To estimate the prevalence of self-reported diabetes and hypertension and their absolute numbers in Brazil. METHODS: Data from 54,369 individuals aged >18 years, interviewed by the Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico (VIGITEL - Telephone-based Surveillance of Risk and Protective Factors for Chronic Diseases), conducted in 27 Brazilian state capitals in 2006, and who responded positively to questions about high blood pressure and diabetes, were analyzed. Percentages of self-reported hypertension and diabetes, estimated in the sample, were projected to the Brazilian population, according to age, sex and nutritional status, using the direct standardization method. RESULTS: Prevalence of diabetes was 5.3% higher in women (6.0% vs. 4.4%), varying from 2.9% in Palmas (Northern Brazil) to 6.2% in São Paulo ( Southeastern Brazil). Prevalence of hypertension was 21.6% (21.3; 22.0) higher in women (24.4% vs. 18.4%), varying from 15.1% in Palmas to 24.9% in Recife (Northeastern Brazil). Prevalences increased with age and nutritional status. It was estimated that there were 6,317,621 adults who reported having diabetes and 25,690,145 adults who reported having hypertension in Brazil. CONCLUSIONS: Prevalence of self-reported diabetes and hypertension are high in Brazil. Monitoring of these and other health conditions can be performed using strategies such as the VIGITEL, especially if followed by validation studies, aiming to generalize results