Abstract
The glutathione S-transferases (GSTs) are involved in the metabolism of many xenobiotics, including an array of environmental carcinogens, pollutants, and drugs. Genetic polymorphisms in these genes may lead to inter- individual variation in susceptibility to various diseases. In the present study, GSTM1 and GSTT1 polymorphisms were analysed using a multiplex polymerase chain reaction in 500 normal individuals from Delhi. The frequency of individuals with GSTM1 and GSTT1 null genotypes were 168 (33.6%) and 62 (12.4%) respectively, and 54 (10.8%) were having homozygous null genotype for both the genes GSTM1 and GSTT1 simultaneously. The studied population was compared with reported frequencies from other neighbouring state populations, as well as with those from other ethnic groups; Europeans, Blacks, and Asians. The prevalence of homozygous null GSTM1 genotype is significantly higher in Caucasians and Asians as compared to Indian population. The frequency of GSTT1 homozygous null genotypes is also significantly higher in blacks and Asians. We believe that due to large number of individuals in this study, our results are reliable estimates of the frequencies of the GSTM1, GSTT1 in Delhi. It would provide a basic database for future clinical and genetic studies pertaining to susceptibility and inconsistency in the response and/or toxicity to drugs known to be the substrates for GSTs.
Highlights
All organisms are constantly and unavoidably exposed to a large number of foreign chemicals or xenobiotics
In the present study we have examined the polymorphism of GSTM1, GSTT1 genes in normal Delhi population
In the present study complete deletion of both GSTM1 and GSTT1 genotypes is observed in 10.8% individuals and the range in Indian population was between 4.5%-10.8%, whereas Nair et al (1999) did not find any subject with homozygous null genotype for both GSTM1 and GSTT1 from Trivandrum
Summary
All organisms are constantly and unavoidably exposed to a large number of foreign chemicals or xenobiotics Most of these chemical carcinogens are not capable of inducing genetic damage themselves but require metabolic activation to electrophilic proximate carcinogens. The polymorphism in GSTM1 and GSTT1 gene loci is caused by a gene deletion which results in the absence of enzyme activity in individuals with the GSTT1 and GSTM1 null genotypes. These homozygous null polymorphisms of GSTM1 and GSTT1 may lead to wide inter-individual variations in the metabolic activation of chemical carcinogen (Board, 1981). We evaluated the distribution of GSTM1, GSTT1 genotypes in Delhi population and compared it with GST polymorphism frequency in different states of India and with various populations worldwide
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