The hOGG1 Ser326Cys gene polymorphism is associated with decreased insulin sensitivity in subjects with normal glucose tolerance

J Hum Genet. 2006;51(2):124-128. doi: 10.1007/s10038-005-0335-8. Epub 2005 Dec 7.


Increased oxidative stress has been observed to contribute the development of insulin resistance. Oxidative stress is known to increase the conversion of deoxyguanosine (dG) to 8-hydroxy-2'-deoxyguanosine (8-OHdG). Human 8-oxoguanine glycosylase (hOGG1) is the key component responsible for the removal of 8-OHdG from oxidatively damaged DNA. The repair activity of the hOGG1 Ser326Cys gene variant has been demonstrated to be lower than that of the hOGG1 Ser/Ser genotype. Therefore, the possible association of the hOGG1 Ser326Cys gene variant with insulin sensitivity was investigated in 279 normal glucose-tolerant subjects without history of cancer. Allele frequency was 21.5% for the Ser/Ser genotype (n = 60), 45.9% for the Ser/Cys genotype (n = 128), and 32.6% for the Cys/Cys genotype (n = 91). Subjects carrying the Cys/Cys genotype had significantly lower insulin sensitivity levels, assessed by homeostasis model assessment-insulin resistance (HOMA-IR), compared with the Ser/Ser and Ser/Cys genotypes (P < 0.001 and P < 0.001, respectively). In a multiple linear regression analysis, the Cys/Cys genotype was a significant determinant of HOMA-IR, independent of age, sex, body mass index, fasting plasma cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, or hypertension. The present study indicates that the hOGG1 gene Cys/Cys variant is associated with a significant decrease in insulin sensitivity in subjects with normal glucose tolerance.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Body Mass Index
  • DNA Glycosylases / genetics*
  • DNA Primers
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Insulin Resistance / genetics*
  • Linear Models
  • Lipids / blood
  • Male
  • Oxidative Stress / genetics*
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Sex Factors
  • Taiwan


  • DNA Primers
  • Lipids
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human