Influence of glutathione S-transferase polymorphisms on type-2 diabetes mellitus risk

Abstract

ABSTRACT. Glutathione S-transferase (GST) protects cells against oxidative stress. We evaluated the effect of genetic polymorphisms of the GST gene family on the risk of developing type-2 diabetes mellitus and on glycemic control. We also investigated the effects of smoking combined with these polymorphisms on type-2 diabetes mellitus risk. We enrolled 100 type-2 diabetes mellitus patients and 100 healthy controls matched for age, gender and origin, from the Sinai area of Egypt. Fasting serum glucose, HbA 1c and lipid profiles were determined. Two polymorphisms were identified by multiplex PCR within the GST genes: GSTM1 and GSTT1. The proportion of the GSTT1-and GSTM1-null genotypes was significantly greater in diabetic patients when compared to controls. Patients carrying both null polymorphisms had a 3.17-fold increased risk of having type-2 diabetes mellitus compared to those with normal genotypes of these two genes (P = 0.009). Additionally, patients with the GSTT1-null genotype had higher levels of triglycerides and very low-density lipoprotein cholesterol compared to those with the ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 10 (4): 3722-3730 (2011) Influence of GST polymorphisms on type-2 DM risk 3723 GSTT1-present genotype. On the other hand, patients with the GSTM1-null genotype had significantly higher levels of HbA 1c and significantly higher diastolic blood pressure compared to those with the GSTM1-present genotype. The interaction between these genotypes and smoking status was not significant. These results give evidence that the GSTT1-and GSTM1-null genotypes, alone or combined, are associated with increased risk of type-2 diabetes mellitus, regardless of smoking status.Only the GSTM1-null genotype had an effect on glycemic control.

Genetic polymorphisms of the CYP1A1, GSTM1, and GSTT1 enzymes and their influence on cardiovascular risk and lipid profile in people who live near a natural gas plant

“…Furthermore, unlike other studies in non-European populations, GSTT1 positive allele in our study was associated with hypertriglyceridemia (31)(32)(33).…”

Genetic Polymorphisms of GSTM1 and GSTT1 Genes in Delhi and Comparison with other Indian and Global Populations

“…Number of female smokers was very less, so it was not possible to compare the results between both the genders. No significant differences were observed between smokers and non-smokers, alcoholic and non-alcoholic individuals, tobacco chewers and non-chewers, carrying homozygous GSTM1/GSTT1/GSTM1T1 null genotype (p>0.05) ( Anantharaman, 2007;Buch et al, 2002;Nair et al, 1999 South Indians c 1744 485 (27.8)** 242 (13.9) 136 (7.8) Naveen et al, 2004;Samson, 2007;Shehnaz et al, 2011;Sreelekha et al, 2001;Suneetha, 2011;Vettriselvi et al, 2006;Vijayalakshmi et al, 2005 East Indians d 67 18(27.0) 9 (13.0) Sikdar et al, 2005 Central Indians e 282 99 (35.1) 37 (13.0) Devi et al, 2008 North Nair et al, 1999;Singh et al, 2009 Blacks b 3008 960 (31.9) 744 (24.9)* 298 (9.9)* Adams et al, 2003;Benzamin et al, 2011;Coutinho et al, 2010;Dandara et al, 2002;Lavender et al, 2009;Masimirembwa et al, 1998;Millikan et al, 2000;Rossini et al, 2002 Caucasians c 2674 1064/2232 (47.7)* 448/2674 (16.7) 31 (9.3) Amer et al, 2011;Baranova et al, 1997;Chen et al, 1996;D'Alo et al, 2004;Gsur et al, 2001;Kargas et al, 2003;Millikan et al, 2000;Mitrunen et al, 2001;Steinhoff et al, 2000;Welfare et al, 1999 Asians 1). The frequency distribution of GSTM1 and GSTT1 alleles were compared between different states of India and other populations all over the world (Table 2 and 3).…”

Genetic Polymorphism of Glutathione-S-Transferase Gene (GSTP1) in Type 2 Diabetes Mellitus Patients in Basra Province/Iraq

“…In an Egyptian study (Amer et al,2011) it has been found that the presence of the allele of valine in the GSTP1 gene in T2DM patients was higher than that found in controls groups, the difference was considered significant when compared to Ile allele. The presence of the heterozygous mutant allele of GSTP1 was found in patient subjects more than in the healthy control .The GSTP1 homozygous mutant allele was not found in T2DM patient and control.…”