The impact of detoxifying and repair gene polymorphisms and the levels of serum ROS in the susceptibility to multiple sclerosis

Abstract

Objective Multiple sclerosis (MS) is an autoimmune neurodegenerative disease with unknown etiology. Oxidative stress (OS) has been implicated to play a role in its cause; therefore, antioxidants and repair systems may help in restoring oxidant-antioxidant balance. Since polymorphisms in DNA repair genes can result in reduced DNA repair capacity, it is important to investigate its association with OS products to demonstrate the impact of individual susceptibility. Our aim is to examine whether a defect in one of the detoxifying and DNA repair enzyme systems could explain the association between MS and exposure to OS products. Methods We investigated the association of polymorphisms in the metabolizing and DNA repair genes with serum Reactive Oxygen Species (ROS) levels. Gene polymorphisms were analyzed by simultaneous multiplex and Restriction Fragment Length Polymorphism Polymerase Chain Reaction and serum ROS levels were detected. Results OGG1 Ser/Cys and Ser/Cys + Cys/Cys genotypes had higher MS risk. XRCC1 Arg/Gln + Gln/Gln genotype increased the risk of MS. Conclusions Our data suggested that OGG1 Ser326Cys gene polymorphism is a major genetic factor involved in the development of MS. Smoking is also a pivotal confounding factor for subjects with mutant genotypes of XRCC1 Arg399Gln. Further studies are needed to reaffirm our results.