Glutathione S-transferase polymorphisms (GSTM1/GSTT1) outcomes in clinical profile and treatment responsiveness among Tunisian cohort of Parkinson's disease.

Abstract

Glutathione S-transferases are involved in the oxidative stress which contributes to the pathogenesis of Parkinson's disease (PD). our aim was to investigate the influence of GSTM1 and GSTT1 polymorphisms on the clinical features and treatments outcomes among PD Tunisian patients. We included 300-PD patients followed in neurology department at Razi-University-hospital. GSTM1 and GSTT1 were screened using PCR methods. Correlation between the clinical phenotype and the genotypes was then assessed after adequate parameters adjustment. Individuals carrying inactive GSTT1/GSTM1 were estimated to have 2.5-fold higher risk of developing PD, p = 0.035. The demographic and clinical baseline analysis of GSTM1 polymorphism revealed significant association between the inactive gene and development of tremor as first symptoms (p = 0.046), further, it was correlated to asymmetric start (p = 0.044). The evaluation of the impact of GSTM1/GSTT1 activity among PD at last follow-up revealed the significant variability of motor impairment among cases carrier of the active genes (p = 0.048). As patients with inactive GSTM1/GSTT1 had higher UPDRS-III score. Additionally, higher frequency of cases with good treatment responsiveness was reported among PD with active GSTM1/GSTT1 (p = 0.038).No motor complications were observed among PD by considering the GSTs genotypes (p > 0.05). Finally, we noted significant impairment of memory among cases with inactivate GSTs (p = 0.04), attention deficit (p = 0.013) and impaired judgement (p = 0.0031). This study represents one of the most comprehensive and extensive investigation to date regarding the influence of GSTT1/GSTM1 genotype among PD patients.We speculate that the impact of GSTT1/GSTM1 on PD progression may occur through a cumulative effect, potentially not manifesting during the initial PD stages. Further studies are necessary to validate our conclusions.