The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes.

摘要: Genetic association studies are viewed as problematic and plagued by irreproducibility1. Many associations have been reported for type 2 diabetes2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17, but none confirmed in multiple samples with comprehensive controls. We evaluated 16 published genetic to diabetes related sub-phenotypes using a family-based design control population stratification, replication increase power. were able confirm only one association, that of the common Pro12Ala polymorphism peroxisome proliferator-activated receptor-γ (PPARγ) diabetes. By analysing over 3,000 individuals, we found modest (1.25-fold) significant (P=0.002) risk associated more proline allele (∼85% frequency). Moreover, our results resolve controversy about variation PPARγ. An initial study threefold effect12, four five subsequent publications18,19,20,21,22 failed association. All six consistent odds ratio describe. The data implicate inherited PPARγ pathogenesis Because occurs at such high frequency, its effect translates into large attributable risk—influencing much 25% general population.