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Influence of glutathione S-transferase polymorphisms (GSTT1, GSTM1, GSTP1) on type-2 diabetes mellitus (T2D) risk in an endogamous population from north India

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Abstract

Glutathione S-transferases (GSTs) belong to a group of multigene and multifunctional detoxification enzymes, which defend cells against a wide variety of toxic insults and oxidative stress. Oxidative stress leads to cellular dysfunction which contributes to the pathophysiology of diseases such as cancer, atherosclerosis, and diabetes mellitus. It is important to assess whether the glutathione S-Transferase (GSTT1, GSTM1 and GSTP1) genotypes are associated with type 2 diabetes mellitus as deletion polymorphisms have an impaired capability to counteract the oxidative stress which is a feature of diabetes. GSTT1, GSTM1 and GSTP1 gene polymorphisms were analysed in 321 patients and 309 healthy controls from an endogamous population from north India. An association analysis was carried out at two levels (a) individual genes and (b) their double and triple combinations. The proportion of GSTT1 and GSTM1 null genotypes was higher in diabetics compared to controls (GSTT1 30.8 vs. 21.0 %; GSTM1 49.5 vs. 27.2 %). The frequency of the null genotype at both loci was higher in diabetics (19.6 vs. 7.8 %) leading to an odds ratio of 2.90 (CI 1.76–4.78, P < 0.0001). At GSTP1locus, patients had a higher frequency of the V/V genotype (15.6 vs. 7.5 %) and significant susceptible odds ratio (2.56, CI 1.47–4.48, P < 0.001). A combination of null genotypes at GSTT1 and GSTM1 loci and V/V genotype of GSTP1 locus showed highest odds ratio (9.64, CI 1.53–60.63, P < 0.01). Overall this study highlights that GST genes may play an important role in the pathogenesis of type 2 diabetes. The risk is higher in individuals carrying more than one susceptible genotype at these loci. The potential role of GST polymorphisms as markers of susceptibility to type 2 diabetes needs further investigations in a larger number of patients and populations.

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Acknowledgments

This paper is dedicated to Late Prof S.S.Papiha who was instrumental in the sample collection. We acknowledge the help and support of local communities and all the participants.

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  1. Antarpreet Kaur

    Present address: University of Connecticut Health Center, Farmington, CT, USA

Authors and Affiliations

  1. Human Genomics Laboratory, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, LE11 3TU, UK

    Sarabjit S. Mastana, Rachel Hale & Martin R. Lindley

  2. Government Hospital, Sangrur, Punjab, India

    Antarpreet Kaur

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  1. Sarabjit S. Mastana
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  2. Antarpreet Kaur
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Correspondence to Sarabjit S. Mastana.

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Mastana, S.S., Kaur, A., Hale, R. et al. Influence of glutathione S-transferase polymorphisms (GSTT1, GSTM1, GSTP1) on type-2 diabetes mellitus (T2D) risk in an endogamous population from north India. Mol Biol Rep 40, 7103–7110 (2013). https://doi.org/10.1007/s11033-013-2833-7

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