Progression of multiple sclerosis is associated with gender differences in glutathione S-transferase P1 detoxification pathway.

The impact of glutathione S-transferases (GSTs) detoxification pathway on complex pathogenesis and heterogeneity of clinical findings in multiple sclerosis (MS), particularly the exact correlation between indicators of clinical severity and different GST genotypes, has not yet been fully elucidated. The aim of the study was to assess the relationship between disability level in multiple sclerosis (estimated by Kurtzke Expanded Disability Status Scale), disease progression (estimated by Multiple Sclerosis Severity Score), the level of brain atrophy and lesion load (determined by MRI) and detoxification status (analyzing glutathione S-transferase P1, GSTP1, genotype profile), in a group of 58 MS patients and 68 age/gendermatched controls. The results present the first evidence on significantly higher frequency of GSTP1 C341T polymorphism (C-T transition) in healthy subjects compared to MS patients, suggesting it may act as a moderating factor in developing MS clinical phenotype. Gender-dependent distribution of the C341T polymorphism was found in both MS patients and controls, with higher frequency of C-T transition in females. In addition, preliminary data showed higher proportion of male MS patients with higher median MSSS scores, as well as lower brain atrophy level and lesion load in MS patients carrying the C341T mutation. Observed gender difference in distribution of the C341T polymorphism in MS patients, as well as in disease progression, suggests that GSTP1 detoxification pathway occurs in a gender-dependent manner and could therefore add to clinical severity in male MS patients.