Sexual dimorphism in xenobiotic genetic variants-mediated risk for Parkinson's disease.

The vulnerability of dopaminergic neurons to environmental exposures in sporadic Parkinson's disease (PD) has been attributed to altered detoxification by xenobiotic metabolizing genes. Hence, we investigated the influence of genetic polymorphisms in xenobiotic metabolic pathway (CYP1A1 m1, CYP1A1 m2, CYP1A1 m4, COMT p.H108L, GSTT1, and GSTM1) on the susceptibility to PD. We used PCR-RFLP for CYP1A1 and COMT genotyping; multiplex-PCR for GSTT1 and GSTM1 deletion analysis; and spectrophotometric methods to evaluate the oxidative stress markers. Results showed association of CYP1A1 m1 (OR: 2.38, 95 % CI: 1.76-3.22) and COMT p.H108L (OR: 2.08 95 % CI: 1.56-2.77) polymorphisms with risk for PD. Male patients carrying combination of COMT p.H108L and CYP1A1 m1 variant alleles showed an early onset of the disease. There was a significant increase in oxidative stress makers such as malondialdehyde and protein carbonyls; and decrease in glutathione levels in PD cases compared to controls (P < 0.05). To conclude, CYP1A1 m1, COMT p.H108L polymorphisms were associated with PD risk, and sexual dimorphism was observed in these associations.