Impact of Tobacco on Glutathione S Transferase Gene Loci of Indian Ethnics

Abstract

Background: Tobacco contains agents which generate various potent DNA adducts that can cause gene mutations. Production of DNA adducts may be neutralized by glutathione S transferase (GST) along with other phase I and phase II enzyme systems. The existence of null type of GST among the population increases the susceptibility to various disorders and diseases. The present study focuses on the impact of high tobacco usage and possible null type mutation in GST loci. Methods: Genotypes of GST were detected by multiplex polymerase chain reaction in unrelated 504 volunteers of high tobacco using natives of Gujarat. Allelic frequencies were calculated using Statistical Package for Social Studies-16 software. Hardy Weinberg Equilibrium (HWE) was calculated using Chi square test. Two sided Fisher's significance test was used to compare allelic frequencies of different populations. Results: The frequency of homozygous null genotype of GSTM1 and GSTT1 were 20% (95% CI 16.7-23.9) and 35.5% (95% CI 31.4-39.9) respectively. The GSTM1 and GSTT1 null allele frequency distribution in the Gujarat population was significantly deviating from HWE. GSTT1 null frequency of Gujaratians was significantly higher and different to all reported low tobacco using Indian ethnics, while GSTM1 was not differing significantly. Conclusion: Tobacco usage significantly influences the rate of mutation and frequency of GSTT1 and M1 null types among the habituates. The rate of mutation in GSTT1 loci was an undeviating response to the dose of tobacco usage among the population. This mutational impact of tobacco on GSTT1 postulates the possible gene -environment interaction and selection of null genotype among the subjects to prone them under susceptible status for various cancers and even worst to cure the population with GSTT1 dependent drugs.

C332C Genotype of Glyoxalase 1 and its Association with Late Diabetic Complications

“…Moreover, the genotype frequencies of Glo1 polymorphism were deviating from HardyWeinberg equilibrium (X 2 = 39.62 and p = 0.5 for type 1; X 2 = 54.42 and p = 0.56 for type 2 diabetes) [ 25 ] . This, for example, could be due to recent somatic mutations, which have not attained null alleles [ 26 ] . In addition, only Caucasian subjects were enrolled while no other genetic background was investigated.…”

Association of genetic polymorphism of glutathione S-transferases with colorectal cancer susceptibility in snuff (Naswar) addicts

“…We found no association of GSTP1 variant genotypes with colorectal cancer risk (OR=1.077, 95% CI: 0.580−1.999). On contrary, other studies reported a significant association between GSTP1 variant genotypes and colorectal cancer risk (Kassab et al, 2014;Lalosevic et al, 2019;Matakova et al, 2009;Senthilkumar and Thirumurugan, 2012;Wang et al, 2011). While Hezova et al (2012) have reported a decreased risk of GSTP1 heterozygote genotype (Ile105Val) and association with colorectal cancer (Hezova et al, 2012).…”