The role of GSTM1, GSTT1, GSTP1, and OGG1 polymorphisms in type 2 diabetes mellitus risk: a case-control study in a Turkish population |
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Authors: | Gönül Nüvit Kadioglu Ela Kocabaş Neslihan Aygün Ozkaya Mesut Karakaya Ali Esat Karahalil Bensu |
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Affiliation: | Refik Saydam National Health Public Agency, Toxicology Department, National Poison Center, Ankara, Turkey. nuvitgonul@gmail.com |
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Abstract: | The aim of the present study was to investigate the role of some polymorphisms in GSTs (GSTM1, GSTT1 and GSTP1) which are very important protective mechanisms against oxidative stress and in OGG1 gene which is important in DNA repair, against the risk of type 2 diabetes mellitus (T2DM). 127 T2DM and 127 control subjects were included in the study. DNA was extracted from whole blood. Analyses of GSTM1 and GSTT1 gene polymorphisms were performed by allele specific PCR and those of GSTP1 Ile105Val and OGG1 Ser326Cys by PCR-RFLP. Our data showed that GSTM1 null genotype frequency had a 2-6 times statistically significant increase in a patient group (OR=3.841, 95% CI=2.280-6.469, p<0.001) but no significance with GSTT1 null/positive and GSTP1 Ile105Val genotypes was observed. When T2DM patients with OGG1 Ser326Cys polymorphism were compared with patients with a wild genotype, a 2-3 times statistically significant increase has been observed (OR 1.858, 95% CI=1.099-3.141, p=0.021). The combined effect of GSTM1 null and OGG1 variant genotype frequencies has shown to be statistically significant. Similarly, the risk of T2DM was statistically increased with GSTM1 null (OR=3.841, 95% CI=2.28-6.469), GSTT1 null+GSTP1 (H+M) (OR=4.118, 95% CI=1.327-12.778) and GSTM1 null+OGG1 (H+M) (OR=3.322, 95% CI=1.898-5.816) and GSTT1 null+OGG1 (H+M) (OR=2.179, 95% CI=1.083-4.386) as compared to the control group. According to our study results, it has been observed that the combined evaluation of GSTM1-GSTT1-GSTP1 and OGG1 Ser326Cys gene polymorphisms can be used as candidate genes in the etiology of T2DM, especially in the development of T2DM. |
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Keywords: | BMI, body mass index DBP, diastolic blood pressure DM, diabetes mellitus DNA, deoxyribonucleic acid GSTs, glutathione S-transferases GSTT1, glutathione S-transferase theta 1 GSTM1, glutathione S-transferase-mu 1 GSTP1, glutathione S-transferase-pi 1 H, heterozygous HOMA-R, homeostatic model assessment-insulin resistance index MBP, mean blood pressure M, mutant OR, odds ratio OGG1, 8-oxoguanine-DNA glycosylase 1 PCR polymerase chain reaction RFLP, restriction fragment length polymorphism ROS, reactive oxygen species SBP, systolic blood pressure T2DM, type 2 diabetes mellitus W, wild WHO, World Health Organization |
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