Comparative frequency distribution of glutathione S-transferase mu (GSTM1) and theta (GSTT1) allelic forms in Himachal Pradesh population

Abstract

Abstract Background Glutathione S-transferases (GSTs) are a class of important Phase II detoxification enzymes that catalyze the conjugation of glutathione and xenobiotic compounds (environmental carcinogens, pollutants and drugs) to protect against oxidative stress. GSTT1 and GSTM1 genetic polymorphisms have been extensively studied, and null genotypes or homozygous deletions have been reported in various populations. Previous studies have suggested that those who are homozygous null at the GSTM1 or GSTT1 loci are more susceptible and have a higher risk of cancers linked to environmental pollutants and drug-induced toxicity. Our study focused on GSTM1 and GSTT1 null allele frequency in the Doon population of Himachal Pradesh (India) with a comparison across other Inter and Intra-Indian ethnic groups to predict variation in the possible susceptible status. Material and methods Genomic DNA samples were extracted from 297 healthy unrelated individuals by a ReliaPrep™ Blood gDNA Miniprep kit (Promega, USA), and genotyped for allelic variation in GSTM1 and GSTT1 genotypes by multiplex polymerase chain reaction. Fisher's exact test was applied using SPSS.20 to analyze the genotypic distribution of GSTM1 and GSTT1 null alleles in male and female of Doon region (Solan) Himachal Pradesh. Results In our study, the frequency distribution of the homozygous null genotypes of GSTM1, GSTT1 individually as well as combined was found as 33.3%, 32% and 9%, respectively. Upon gender-wise comparison, a non-significant distribution (p > 0.05) for null genotypes of GSTM1 (32.8% and 35.4%, OR-0.77, 95% CI 0.42–1.41), GSTT1 (33.2% and 27.7%, OR-1.12, 95% CI 0.63–2.0) individually and combined GSTM1 and GSTT1 (10.8% and 3.7%, OR-0.31, 95% CI 0.07–1.42) were observed in studied population. Conclusions In our studied population, the frequency of GSTM1 null genotypes was found deviated from Inter- and Intra-Indian ethnic groups. However, the frequency of homozygous null type of GSTT1 was not significantly different, when compared to previous Indian studies, comparison with global ethnic groups showed deviation. Thus, our study has highlighted possible susceptibility risk to various xenobiotics in the Doon population of Himachal Pradesh, India.

Keywords

• GSTM1
• GSTT1
• Polymerase chain reaction
• Polymorphism
• Genotype
• Allele