title: The hOGG1 Ser326Cys gene polymorphism is associated with decreased insulin sensitivity in subjects with normal glucose tolerance.
abstract: 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.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
authors.forename: Chiao-Ling
authors.initials: CL
authors.lastname: Wang
authors.affiliation: Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, 100 Shih-Chuan 1st Rd, Kaohsiung, 80708, Taiwan, ROC.
authors.forename: Ming-Chia
authors.initials: MC
authors.lastname: Hsieh
authors.affiliation: Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, 100 Shih-Chuan 1st Rd, Kaohsiung, 80708, Taiwan, ROC.
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Hsin
authors.affiliation: Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, 100 Shih-Chuan 1st Rd, Kaohsiung, 80708, Taiwan, ROC.
authors.forename: Hsing-Yi
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, 100 Shih-Chuan 1st Rd, Kaohsiung, 80708, Taiwan, ROC.
authors.forename: Kun-Der
authors.initials: KD
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
authors.forename: Chao-Sheng
authors.initials: CS
authors.lastname: Lo
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
authors.forename: Zhao-Hong
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Shyi-Jang
authors.initials: SJ
authors.lastname: Shin
mesh_terms: 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
chemical_list: D017931:DNA Primers; D008055:Lipids; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human