The Ser(326)Cys Polymorphism of 8-Oxoguanine Glycosylase 1 (OGG1) Is Associated with Type 2 Diabetes in Mexican Americans

Abstract

Objective: Human 8-oxoguanine glycosylase 1 (OGG1) excises oxidatively damaged promutagenic base 8-oxoguanine, a lesion previously observed in a rat model of type 2 diabetes (T2DM). The objective of the present study is to determine whether genetic variation in OGG1 is associated with type 2 diabetes (T2DM) in a Mexican American cohort. Methods: Ten SNPs including two tagging SNPs (rs1052133, rs2072668) across the OGG1 gene region were selected from the Hapmap database and genotyped in the entire cohort (n = 670; 29% diabetes; 39 families) by TaqMan assay. Association analyses between the SNPs and T2DM were performed using the measured genotype approach as implemented in the program SOLAR. Results: Of the ten SNPs genotyped, only five were polymorphic. The minor allele frequencies of these 5 SNPs ranged from 1–38%. Of the SNPs examined for association, the Ser(326)Cys (rs1052133) exhibited significant association with T2DM (p = 0.016) after accounting for age and sex effects. Another intronic variant (rs2072668), which was in strong linkage disequilibrium (r² = 0.96) with Ser(326)Cys also exhibited significant association with T2DM (p = 0.031). Conclusions: These results suggest for the first time that the variants in OGG1 could influence diabetes risk in these Mexican American families and support a role for alterations of OGG1 in the pathogenesis of T2DM.

Oxidative DNA damage in disease—Insights gained from base excision repair glycosylase‐deficient mouse models

“…In this regard, the Ser326Cys mutation has been associated with human lung squamous cell carcinomas [Lu et al, 1997;Chevillard et al, 1998;Sugimura et al, 1999;Wikman et al, 2000;Le Marchand et al, 2002;Paz-Elizur et al, 2003;Okasaka et al, 2009], orolaryngeal [Elahi et al, 2002], esophageal [Xing et al, 2001], kidney [Chevillard et al, 1998;Audebert et al, 2000Audebert et al, , 2002, and gastric cancers [Farinati et al, 2008]. Recently, two studies have also reported an association between the Ser326Cys mutation and increased body mass index and susceptibility to Type II diabetes [Daimon et al, 2009;Thameem et al, 2010].…”

The role of GSTM1, GSTT1, GSTP1, and OGG1 polymorphisms in type 2 diabetes mellitus risk: A case–control study in a Turkish population

“…To our knowledge, only two papers are presented up to date. In a recent study of Thameem et al (2010) the association of a genetic variation in OGG1 with type T2DM was investigated in a Mexican American cohort. The results of said study demonstrated a significant association of Ser326Cys genotype with T2DM.…”

Hyperactivation of Akt/mTOR and deficiency in tuberin increased the oxidative DNA damage in kidney cancer patients with diabetes

“…Our recent published data showed a significant association between mutations in OGG1 (Ser 326 to Cys) and type II diabetes in genomic DNA isolated from blood mononuclear cells of diabetic patients. This suggests that OGG1 plays an important role in regulating the oxidative DNA damage in diabetic patients [26]. …”