Multi-locus candidate gene polymorphisms and risk of type 2 Diabetes Mellitus: population-based, prospective genetic analysis

Abstract

Type 2 diabetes (T2D) is a complex disease characterized by insulin resistance and impaired pancreatic ²-cell function. In T2DM, a variety of environmental and genetic factors play a major role in the clinical expression of disease. The most frequent form of the disease is late onset T2DM, which may be characterized by a polygenic syndrome. Polymorphisms in candidate genes associated with glucose homeostasis, lipids metabolism, cardiovascular risk factors or pro-inflammatory cytokines may represent potential risk factors to T2DM. The aim of this study was to assess the relationship between a panel of well characterized genetic variants in 36 candidate genes and the incidence of type 2 diabetes mellitus. We evaluated a panel of 55 candidate genes polymorphisms in a total of 24,309 Caucasian women free of diabetes at baseline, who have participated of the Women's Health Study during median follow up of 10 years. Cox proportional-hazards models were constructed to compared the incidence of T2DM according to the different genotypes. (AU)