The hOGG1 Ser326Cys gene polymorphism is associated with decreased insulin sensitivity in subjects with normal glucose tolerance.
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.
Wang
Chiao-Ling
CL
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
Hsieh
Ming-Chia
MC
Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, 100 Shih-Chuan 1st Rd, Kaohsiung, 80708, Taiwan, ROC.
Hsin
Shih-Chieh
SC
Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, 100 Shih-Chuan 1st Rd, Kaohsiung, 80708, Taiwan, ROC.
Lin
Hsing-Yi
HY
Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, 100 Shih-Chuan 1st Rd, Kaohsiung, 80708, Taiwan, ROC.
Lin
Kun-Der
KD
Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, 100 Shih-Chuan 1st Rd, Kaohsiung, 80708, Taiwan, ROC.
Lo
Chao-Sheng
CS
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
Chen
Zhao-Hong
ZH
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
Shin
Shyi-Jang
SJ
Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, 100 Shih-Chuan 1st Rd, Kaohsiung, 80708, Taiwan, ROC. sjshin@kmu.edu.tw.|Graduate Institute of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC. sjshin@kmu.edu.tw.
D000367:Age Factors; D015992:Body Mass Index; D045647:DNA Glycosylases / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D016014:Linear Models; D008055:Lipids / Q000097:blood; D008297:Male; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012737:Sex Factors; D013624:Taiwan
D017931:DNA Primers; D008055:Lipids; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human