Kimberly C Paul1, Janet S Sinsheimer2, Myles Cockburn3, Jeff M Bronstein4, Yvette Bordelon4, Beate Ritz5. 1. Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA. 2. Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, CA, USA; Departments of Human Genetics and Biomathematics, David Geffen School of Medicine, Los Angeles, CA, USA. 3. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, CA, USA. 4. Department of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA. 5. Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA. Electronic address: britz@ucla.edu.
Abstract
OBJECTIVE: To investigate three expression-altering NFE2L2 SNPs and four PPARGC1α 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 (β = 0.095; p = 0.0004). None of the PPARGC1α SNPs were marginally associated with PD risk. We estimate statistical interactions between MB/PQ and PPARGC1α 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). PPARGC1α rs6821591 was also associated with faster motor symptom progression as measured with the UPDRS-III (β = 0.234; p = 0.001). CONCLUSION: Our study provides support for the involvement of both NFE2L2 and PPARGC1α in PD susceptibility and progression, marginally and through pathways involving MB/PQ exposure.
OBJECTIVE: To investigate three expression-altering NFE2L2 SNPs and four PPARGC1α previously implicated SNPs and pesticides on Parkinson's disease (PD) risk and symptom progression. METHODS: In 472 PDpatients 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:NFE2L2rs6721961 T allele was associated with a reduced risk of PD (OR = 0.70, 95% CI = 0.53, 0.94) and slower cognitive decline (β = 0.095; p = 0.0004). None of the PPARGC1α SNPs were marginally associated with PD risk. We estimate statistical interactions between MB/PQ and PPARGC1α 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). PPARGC1α rs6821591 was also associated with faster motor symptom progression as measured with the UPDRS-III (β = 0.234; p = 0.001). CONCLUSION: Our study provides support for the involvement of both NFE2L2 and PPARGC1α in PD susceptibility and progression, marginally and through pathways involving MB/PQ exposure.
Authors: Bin Zheng; Zhixiang Liao; Joseph J Locascio; Kristen A Lesniak; Sarah S Roderick; Marla L Watt; Aron C Eklund; Yanli Zhang-James; Peter D Kim; Michael A Hauser; Edna Grünblatt; Linda B Moran; Silvia A Mandel; Peter Riederer; Renee M Miller; Howard J Federoff; Ullrich Wüllner; Spyridon Papapetropoulos; Moussa B Youdim; Ippolita Cantuti-Castelvetri; Anne B Young; Jeffery M Vance; Richard L Davis; John C Hedreen; Charles H Adler; Thomas G Beach; Manuel B Graeber; Frank A Middleton; Jean-Christophe Rochet; Clemens R Scherzer Journal: Sci Transl Med Date: 2010-10-06 Impact factor: 17.956
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