Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population

Abstract

Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% heterozygous AG and 25.24% homozygous mutant GG. The frequency of GSTP1-A allele was 50.24% versus 49.76% for the GSTP1-G allele. The distribution of these three genes was homogeneous between men and women (p > 0.05). We found no statistical association between the presence of a particular profile of GSTM1 or GSTT1 with the genotypes of GSTP1 (p > 0.05). Nevertheless, we noticed that the majority of the individuals harboring the GSTM1-present or the GSTT1-present harbor also the GSTP1-AG genotype. In addition, the triple genotype GSTM1present/GSTT1-present/AG was the most frequent with 25.2%. Our findings will facilitate future studies regarding genetic associations of multifactorial diseases and pharmacogenetic, thus opening the way to personalized medicine in our population.

Pharmacogenomic Profile of Amazonian Amerindians

“…The GSTT1 belong to the super family of glutathione S-transferases. These enzymes are implicated in the second-phase metabolism of several compounds, such as anticancer and xenobiotic substances [ 37 ]. Polymorphisms in the GSTT1 gene show significant frequency differences among distinct ethnic groups: East Asians present the highest frequencies worldwide for GSTT1 deletions [ 38 ], which could implicate in higher interindividual variability in pharmacotherapy responses and susceptibility to various diseases, especially those of hepatological disorders [ 39 ].…”

Analysis of Very Important Pharmacogenomics Variants in the Chinese Lahu Population

“…Their polymorphism has been reported to be closely related to alcohol metabolism, 29 tobacco metabolism, 30 and carcinogen metabolism. 31 What is more, there are population differences, especially in Asia with the other states. Lahu and CHB were found to be two close populations.…”

Nutritional Sources and Anticancer Potential of Phenethyl Isothiocyanate: Molecular Mechanisms and Therapeutic Insights

“…Genetic polymorphisms, particularly in genes related to detoxification and drug metabolism pathways (e.g., GSTM1, GSTT1), can influence the efficacy of PEITC. [ 199 ] Personalized medicine approaches should be considered, where genetic profiling of patients can guide the use of PEITC; stratifying patients based on their genetic makeup may help in identifying those who are most likely to benefit from PEITC treatment. [ 199 ]…”