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 Ser 326 Cys gene variant has been demonstrated to be lower than that of the hOGG1 Ser/ Ser genotype. Therefore, the possible association of the hOGG1 Ser 326 Cys 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.

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

“…8-OHdG in turn would promote an increase in G:C ] T:A transversions, DNA damage and loss of pancreatic ␤ -cell, thereby contributing to the development of T2DM. In support of this notion, a significant association has recently been reported between Ser(326)Cys variant of OGG1 and type 2 diabetes [19] and decreased insulin sensitivity in patients with normal glucose tolerance test [6] . Further confirmatory studies of this genetic association and/or functional studies are required to support the observed association between the Ser(326)Cys variant and T2DM.…”

“…Carriers of Cys/Cys were found to have lower OGG1 activity and impaired ability to repair 8-OHdG than the carriers of Ser/Ser allele, thus contributing to the cancer risk [5] . Recently, the Ser(326)Cys variant was reported to be associated with decreased insulin sensitivity in subjects with normal glucose tolerance suggesting that genetic alterations in OGG1 may contribute to insulin resistance and potentially T2DM [6] . However, the association between OGG1 polymorphisms and T2DM has not yet been explored.…”

hOGG1 gene polymorphisms and susceptibility to polycystic ovary syndrome

“…Specifically, certain polymorphisms in hOGG1 that are associated with insulin sensitivity or T2MD have been reported, indicating the functional involvement of hOGG1 in the maintenance of normal glucose metabolism (9,20,25). Previous studies have reported an association between oxidative stress and insulin resistance not only in the context of diabetes, but also in nondiabetic individuals and in those with metabolic syndromes (26)(27)(28).…”

“…TNF-α and ROS in turn exacerbate the inflammatory process, resulting in chronic inflammation in PCOS patients. The hOGG1 gene is associated with decreased insulin sensitivity (20), a common feature of certain PCOS patients. Therefore, we hypothesize that a link between the hOGG1 gene and PCOS may exist.…”

Персонифицированное Применение Метформина С Позиции Фармакогенетики (Обзор)

“… èññëåäîâàíèÿõ ïîêàçàíà ñòðîãàÿ àññîöèàöèÿ ïîëè-ìîðôèçìà C977G (Ser326Cys), ÷àñòíîñòè àëëåëþ G (Cys), ñ èíñóëèíîðåçèñòåíòíîñòüþ (ÈÐ) ó ïàöèåíòîâ ñ ïðåäèà-áåòîì [53], ïîâûøåííûìè ïîêàçàòåëÿìè ÈÌÒ è óðîâíåì ãëþêîçû êðîâè [25].…”