Frequency of GSTT1*0 genotype as a non-conjugator phenotype in a group of healthy Iranian people

Abstract

Glutathione S-transferases (GSTs) are dimeric mainly cytosolic enzymes involved in detoxification of many exogenous and endogenous disease-causing electrophilic substrates. GSTs also have critical role in phase II biotransformation of a number of drugs, xenobiotics and industrial chemicals and protect cellular macromolecules. The evidences supported that human GSTT1 contributes in the deactivation of reactive oxygen species which more likely to be effective in inflammatory diseases, ageing and some non-cancer diseases also different types of cancers. The GSTT1 is genetically deleted in a high percentage of the different ethnic groups. Although this gene is highly conserved during evolution, it is indeed surprising that the GSTT1 deleted gene could be found in high incidence of human population. Conjugator and non-conjugator phenotypes are coincident with this deletion (GSTT1*1 and GSTT1*0 genotype).The consequences of this deletion could be involved in some diseases outcome, toxicology and drug resistances. In this study the Real-time PCR assay and a set of hybridization probes was used as a one-step and accurate method to estimate the frequency of GSTT1*0 genotype as a non-functional phenotype in 90 healthy individuals from the province of Isfahan in Iran. GSTT1 genotypes were identified in DNA samples using fluorogenic Real-Time PCR (LightCycler) followed by online melting curve analysis. The incidence of GSTT1*1(wild type) and GSTT1*0(Null type) were 74.5% and 25.5% respectively. No differences in genotypes frequencies were perceived in samples stratified by age and gender P> 0.05. The results were compared with other ethnic groups to get more insight into the frequency differences of defected carcinogens metabolizer gene due to deletion polymorphism of GSTT1. It has been indicated the incidence of GSTT1*0 in this group of Iran showed significant differences with East Asian and some European and American countries P< 0.05.The prevalence of GSTT1 null genotype in the study group from Isfahan province of Iran was slightly higher in comparison with other Iranian ethnic group (Iranian Georgian 15.7%), but this difference was not significant (χ2=1.66, P=0.197). Further experimental investigations are needed to inquiry the clinical implications of GSTT1 genetic polymorphism with consider to significant variability among different ethnicities