Human glutathione s-transferase enzyme gene variations and risk of multiple sclerosis in Iranian population cohort

Abstract

Multiple sclerosis (MS) is an inflammatory disease with unknown etiology. Oxidative stress has been demonstrated to play a role in pathological and inflammatory mechanisms of MS. Cells activate antioxidant processes in response to oxidative stress. Glutathione is one of the antioxidant agents in the brain and serves as a cofactor for glutathione s-transferase (GST) enzymes for detoxifying nerve cells. Among different classes of GST, GSTM1 and GSTT1 are associated with the loss of function due to structural homozygous deletion. The aim of this study is to investigate GSTM1 and GSTT1 null genotypes in an Iranian population.In this study, 270 patients and 250 healthy controls were investigated. Patient's disabilities were assessed by Kurtzke Expanded Disability Status Scale (EDSS) and genotypes were determined by multiplex PCR. Association between genotype and MS, type of MS, gender, and inability level were surveyed.The findings demonstrated a highly significant association between the null genotypes and MS (OR = 6.89 for M1/T1). The combination of two genotypes increased the risk of MS by 6.8 times. The null genotypes were found to be more frequent in women than in men. Moreover, a significant association was observed between the null genotype and EDSS 6–10 (OR = 3.199). No significant association was noticed between MS type and the studied genotypes. According to this study, it can be proposed that people with GSTM1 and GSTT1 deletions are at a higher risk for developing MS, which can be due to a decrease in enzymatic activity and their levels in nerve cells and the brain.