The G/G genotype of a resistin single-nucleotide polymorphism at -420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3.

ABSTRACT: Insulin resistance is a major cause of type 2 diabetes mellitus (T2DM). Resistin, an adipocyte-secreted hormone, antagonizes insulin. Transgenic mice that overexpress the resistin gene (Retn) in adipose tissue are insulin-resistant, whereas Retn (-/-) mice show lower fasting blood glucose, suggesting that the altered Retn promoter function could cause diabetes. To determine the role of RETN in human T2DM, we analyzed polymorphisms in its 5' flanking region. We found that the -420G/G genotype was associated with T2DM (397 cases and 406 controls) (P=.008; adjusted odds ratio = 1.97 [by logistic regression analysis]) and could accelerate the onset of disease by 4.9 years (P=.006 [by multiple regression analysis]). Meta-analysis of 1,888 cases and 1,648 controls confirmed this association (P=.

SUBMITTER: Osawa H 

PROVIDER: S-EPMC1182055 | biostudies-literature | 2004 Oct

REPOSITORIES: biostudies-literature