Influence of GSTP1 rs1695 polymorphism on survival in male patients' amyotrophic lateral sclerosis: a genetic association study in Brazilian population.

ABSTRACT

BACKGROUND: Glutathione S-transferase Pi (GSTP1) enzyme has a major antioxidant effect on the central nervous system (CNS), where it acts against oxidative damage, an established risk factor for amyotrophic lateral sclerosis (ALS). Hence, the purpose of this study was to evaluate a possible relationship between GSTP1 rs1695 polymorphism and the survival rate of male ALS patients, which is the gender more affected by the disease. METHODS AND RESULTS: A case-control study was performed with 56 male ALS patients and 70 healthy male individuals from Midwestern Brazil, which were age-adjusted. GSTP1 rs1695 polymorphism molecular analysis was carried out with restriction fragment length polymorphism. The relationship between ALS patients and GSTP1 rs1695 polymorphism was analyzed using cumulative survival rate as the major outcome, where differences in survival were evaluated through the log-rank test. Our results revealed that mutant genotype (G/G) did not influence the cumulative survival rate of male ALS patients regarding the age of diagnosis (p = 0.5) and time from symptom to diagnosis (p = 0.3). On the other hand, mutant carriers exhibited a significant survival of fewer than 25 months compared to A/A and A/G genotypes that survive more than 100 months (p = 7-E10) in comparison with symptom onset to outcome (p = 0.00006). CONCLUSIONS: In summary, our findings revealed that mutant genotype carriers' male patients had a reduced lifetime, which probably may be resulted from oxidative stress exposure in CNS.