engleski

Glutathione S-transferase polymorphisms: role and sex dimorphisms in multiple sclerosis

Glutathione S-transferases are multiple gene family enzymes participating in phase II drug biotransformation, detoxification, steroidogenesis, and cell signaling. Glutathione S-transferase P1 (GSTP1) is the most important large group of nonhepatical enzymes. Genetic basis for effective enzymatic detoxification of endogenous and exogenous toxins (neurotoxins) considerably contributes to etiopathogenesis of neurodegenerative diseases. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). In this study we investigated glutathione S-transferase P1 (GSTP1) polymorphisms in 54 Croatian MS patients in comparison with 86 age- and gender-matched controls. Distribution and frequencies of GSTP1 genetic variants were not statistically different between MS patients and controls for A313G polymorphism (p=0.228). Analysis of C341T polymorphism showed higher frequencies of the mutant genotypes and a statistical difference between MS patients and controls (p=0.013). The calculated relative risk for mutant TT genotype in MS patients compared with a combined category of CT and CC indicates a worse outcome of GSTP1 polymorphism (OR=5.4359, 95%Cl (0.6604 - 44.7457) in females in comparison with male patients. Correlation between genotype and disability status was not found (p= 0.440). The frequencies of GSTP1 alleles (A, B, C, D) also differed between MS patients and controls. The haplotype GSTP1*A/GSTP1*D showed statistically significant difference between MS patients and controls (p=0.043). Evidence for sex dimorphism for A313G polymorphism was not found (p=0.601). However, higher incidence of C341T polymorphisms was observed in female patients, indicating a possible role of the GSTP1 detoxification pathway in the pathogenesis of multiple sclerosis, in a gender-dependent manner.

glutathione S-transferase P1; multiple sclerosis; polymorphism; sex dimorphism

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