Association of glutathione S-transferase (GSTM1, T1 and P1) gene polymorphisms with type 2 diabetes mellitus in north Indian population

• Main Authors: Bid H, Konwar R, Saxena M, Chaudhari P, Agrawal C, Banerjee M
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2010-01-01
• Series: Journal of Postgraduate Medicine
• Subjects: Genotypes; glutathione S-transferase; oxidative stress; PCR-RFLP; risk factors
• Online Access: http://www.jpgmonline.com/article.asp?issn=0022-3859;year=2010;volume=56;issue=3;spage=176;epage=181;aulast=Bid

<b>Background:</b> Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense. The oxidative stress becomes evident as a result of accumulation of ROS in conditions of inflammation and Type 2 diabetes mellitus (T2DM). The genes involved in redox balance, which determines the susceptibility to T2DM remain unclear. In humans, the glutathione S-transferase (<i>GST</i>) family comprises several classes of GST isozymes, the polymorphic variants of GSTM1<i>,</i> T1 and P1 genes result in decreased or loss of enzyme activity. <b>Aims:</b> The present study evaluated the effect of genetic polymorphisms of the GST gene family on the risk of developing T2DM in the North Indian population. <b>Settings and Design:</b> GSTM1, T1 and P1 polymorphisms were genotyped in 100 T2DM patients and 200 healthy controls from North India to analyze their association with T2DM susceptibility. <b>Materials and Methods:</b> Analysis of GSTM1 and <i>GSTT1</i> gene polymorphisms was performed by multiplex polymerase chain reaction (PCR) and GSTP1 by PCR-Restriction Fragment Length Polymorphism (RFLP). Statistical Analysis: Fisher&#x2032;s exact test and &#967;² statistics using SPSS software (Version-15.0). Results: We observed significant association of GSTM1 null (<i>P</i>=0.004, OR= 2.042, 95&#x0025;CI= 1.254-3.325) and GSTP1 (I/V) (<i>P</i>=0.001, OR= 0.397, 95&#x0025;CI=0.225-0.701) with T2DM and no significant association with <i>GSTT1</i> (<i>P</i>=0.493). The combined analysis of the three genotypes GSTM1 null, T1 present and P1 (I/I) demonstrated an increase in T2DM risk (<i>P</i>= 0.005, OR= 2.431 95&#x0025; CI=1.315-4.496). <b>Conclusions:</b> This is the first study showing the association of a combined effect of GSTM1<i>,</i> T1 and P1 genotypes in a representative cohort of Indian patients with T2DM. Since significant association was seen in GSTM1 null and GSTP1 (I/V) and multiple association in GSTM1 null, T1 present and P1 (I/I), these polymorphisms can be screened in the population to determine the diabetic risk.