NFE2L2, PPARGC1α, and pesticides and Parkinson's disease risk and progression

Objective: To investigate three expression-altering NFE2L2 SNPs and four PPARGC1 alpha previously implicated SNPs and pesticides on Parkinson's disease (PD) risk and symptom progression. Methods: In 472 PD patients and 532 population-based controls, we examined variants and their interactions with maneb and paraquat (MB/PQ) pesticide exposure on PD onset (logistic regression) and progression of motor symptoms and cognitive decline (n = 192; linear repeated measures). Results: NFE2L2 rs6721961 T allele was associated with a reduced risk of PD (OR = 0.70, 95% CI = 0.53, 0.94) and slower cognitive decline (beta = 0.095; p = 0.0004). None of the PPARGC1 alpha SNPs were marginally associated with PD risk. We estimate statistical interactions between MB/PQ and PPARGC1 alpha rs6821591 (interaction p = 0.009) and rs8192678 (interaction p = 0.05), such that those with high exposure and the variant allele were at an increased risk of PD (OR >= 1.30, p <= 0.05). PPARGC1 alpha rs6821591 was also associated with faster motor symptom progression as measured with the UPDRS-III (beta = 0.234; p = 0.001). Conclusion: Our study provides support for the involvement of both NFE2L2 and PPARGC1 alpha in PD susceptibility and progression, marginally and through pathways involving MB/PQ exposure.