Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 173, Issue -, Pages 1-8Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2018.04.004
Keywords
NFE2L2; PPARGC1 alpha; Paraquat Parkinson's disease; Cognition
Categories
Funding
- National Institute of Environmental Health Science [R01-ES010544, U54-ES012078, F32-ES028087]
- National Institute of General Medical Sciences [R01-GM053275]
- National Cancer Institute [R01-CA195218]
- Burroughs Wellcome Fund Population and Laboratory Based Sciences Award
- Veterans Administration Healthcare System (SW PADRECC)
- Levine Foundation
- Parkinson Alliance
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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.
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