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Glutathione S-transferase gene polymorphisms association with disease severity and progression of multiple sclerosis

Glutathione S-transferases (GSTs), a multiple gene family of enzymes participating in detoxification processes, may be involved in the pathogenesis of multiple sclerosis (MS). The aim of this study was to investigate relationship of previously estimated glutathione S-transferase P1 (GSTP1) gene polymorphisms with enzyme activity, disease severity/progression, and magnetic resonance (MR) findings in patients with multiple sclerosis (MS). Our previous study showed a distribution of gene GSTP1 polymorphisms A313G (105Ile/Val) and C341T (114Ala/Val) in 58 MS patients compared with age- and gender-related controls. In this study, disease severity and progression were analyzed using Multiple sclerosis severity score (MSSS). Also, the enzymatic activity of glutathione S-transferase was measured in MS patients, found to be carriers of the mutated alleles i.e. genotypes AG/GG (N = 32) and CT/TT (N = 12). In addition, MS patients with higher MSSS score and presence of mutated alleles were examined using conventional MR techniques. Results obtained by MSSS testing showed that patients carrying the GG mutated genotype have significantly higher median MSSS score than patients with AA or AG genotype, while MS patients carrying the TT mutated genotype had the lowest MSSS scores compared with carriers of CC/CT genotype. Slightly decreased activity of glutathione S-transferase was measured in MS patients-mutation carriers compared with mutation non-carriers and controls. We suggest that analyzed gene polymorphisms of GSTP1, involved in antioxidative protection, may contribute to multiple sclerosis pathogenesis. Also, for the purposes of estimation of disease severity, progression and prognosis, utilization of genotype-phenotype analysis proved to be extremely useful.

multiple sclerosis; glutathione S-transferase; disease

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