Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, China.
Mol Cell Endocrinol. 2010 Aug 30;325(1-2):128-34. doi: 10.1016/j.mce.2010.05.005. Epub 2010 May 16.
hOGG1 protein excises the 8-hydroxy-2'-deoxyguanine (8-OHdG) which is associated with type 2 diabetes mellitus (T2DM). Our aim of this work is to explore whether the polymorphisms of hOGG1 gene are associated with T2DM. We screened the polymorphisms in the 5'-UTR (c.-18G>T, c.-23A>G, c.-45G>A and c.-53G>C) and c.977C>G (Ser326Cys) in exon 7 of hOGG1 gene. A case-control study indicated that c.-23A/G heterozygote was markedly associated with diabetes (P=0.004, OR=2.648, 95%CI=1.355-5.176) and with an increased level of C-peptide (705.00 versus 545.91 pmol/L, P=0.044). Furthermore, a significantly increased risk of T2DM was observed in the subjects carrying heterozygous variant of c.-23A>G and homozygous mutation of Ser326Cys (OR=3.684, 95%CI=1.400-9.697). The promoter activity of the variant allele c.-23G decreased 30-40% in Hela and HEK293 cell lines. In conclusion, the variant c.-23A>G of hOGG1 gene could decrease the gene promoter activity and was a risk factor for T2DM.
hOGG1 蛋白切除与 2 型糖尿病（T2DM）相关的 8-羟基-2'-脱氧鸟嘌呤（8-OHdG）。我们这项工作的目的是探讨 hOGG1 基因的多态性是否与 T2DM 相关。我们筛选了 hOGG1 基因 5'-UTR（c.-18G>T、c.-23A>G、c.-45G>A 和 c.-53G>C）和 c.977C>G（Ser326Cys）外显子 7 中的多态性。一项病例对照研究表明，c.-23A/G 杂合子与糖尿病显著相关（P=0.004，OR=2.648，95%CI=1.355-5.176），并且 C 肽水平升高（705.00 与 545.91 pmol/L，P=0.044）。此外，携带 c.-23A>G 杂合变体和 Ser326Cys 纯合突变的个体发生 T2DM 的风险显著增加（OR=3.684，95%CI=1.400-9.697）。在 Hela 和 HEK293 细胞系中，变体等位基因 c.-23G 的启动子活性降低了 30-40%。总之，hOGG1 基因的变体 c.-23A>G 可降低基因启动子活性，是 T2DM 的危险因素。
