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

Yaya Kassogue,Cheick Bougadari Traore,Kadidiatou Tamboura,Seydou Doumbia,Hind Dehbi,Sellama Nadifi,Sounkalo Dao,Guimogo Dolo,Brehima Diakite,Oumar Kassogue,Zoumana Diarra,Issa Konate

doi:10.1007/s11033-019-05143-5

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 GSTM1-present/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.

Highlights

GSTM1, GSTT1 and GSTP1 belong to the super family of glutathione S-transferases (GSTs)
The GSTT1-null genotype was observed in 41.3% of our participants
There was no statistical difference in the distribution of GSTT1-null genotype according to gender; the frequency in women was 42.5% versus 39.8% in men (X2 = 1.53; p = 0.7) (Table 1)

Summary

Introduction

GSTM1, GSTT1 and GSTP1 belong to the super family of glutathione S-transferases (GSTs) These enzymes are known to play a key role in the metabolism of xenobiotic, anticancer and anti-infectious, through their participation in the second phase of xenobiotic metabolism [1, 2]. GSTs appear to play a signaling role in the activation of cytoprotective genes by inhibiting the jun kinase pathway [3, 4] This detoxification activity is intimately linked to the capacity of each individual, which is itself modulated by individual’s genetic background [5, 6]. We performed the present study to evaluate the genotypic and allelic distribution of these genes in the healthy Malian population. The results from the present study will facilitate future studies such as genetic susceptibility to disease and individual variability to drugs

Methods

Results

Conclusion