title: Gene-environment interactions linking air pollution and inflammation in Parkinson's disease.
abstract: Both air pollution exposure and systemic inflammation have been linked to Parkinson's disease (PD). In the PASIDA study, 408 incident cases of PD diagnosed in 2006-2009 and their 495 population controls were interviewed and provided DNA samples. Markers of long term traffic related air pollution measures were derived from geographic information systems (GIS)-based modeling. Furthermore, we genotyped functional polymorphisms in genes encoding proinflammatory cytokines, namely rs1800629 in TNFα (tumor necrosis factor alpha) and rs16944 in IL1B (interleukin-1β). In logistic regression models, long-term exposure to NO2increased PD risk overall (odds ratio (OR)=1.06 per 2.94μg/m3increase, 95% CI=1.00-1.13). The OR for PD in individuals with high NO2exposure (≧75th percentile) and the AA genotype of IL1B rs16944 was 3.10 (95% CI=1.14-8.38) compared with individuals with lower NO2exposure (<75th percentile) and the GG genotype. The interaction term was nominally significant on the multiplicative scale (p=0.01). We did not find significant gene-environment interactions with TNF rs1800629. Our finds may provide suggestive evidence that a combination of traffic-related air pollution and genetic variation in the proinflammatory cytokine gene IL1B contribute to risk of developing PD. However, as statistical evidence was only modest in this large sample we cannot rule out that these results represent a chance finding, and additional replication efforts are warranted.
authors.affiliation: Department of Health Care Management, College of Health Technology, National Taipei University of Nursing and Health Sciences, 89, Nei-Chiang St. Wan-Hua Dist, Taipei 10845, Taiwan. Electronic address: pcl0807@gmail.com.
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Lee
authors.affiliation: Danish Cancer Society Research Center, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Raaschou-Nielsen
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Lübeck, Germany; Institute of Human Genetics, University of Lübeck, Lübeck, Germany.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Lill
authors.affiliation: Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany; School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology, and Medicine, London, UK.
authors.forename: Lars
authors.initials: L
authors.lastname: Bertram
authors.affiliation: Department of Human Genetics and Biomathematics, David Geffen School of Medicine at UCLA, CA, USA; Department of Biostatistics, Fielding School of Public Health, University of California at Los Angeles, CA, USA.
authors.forename: Janet S
authors.initials: JS
authors.lastname: Sinsheimer
authors.affiliation: Danish Cancer Society Research Center, Denmark.
authors.forename: Johnni
authors.initials: J
authors.lastname: Hansen
authors.affiliation: Department of Neurology, School of Medicine, University of California at Los Angeles, CA, USA; Department of Epidemiology, Fielding School of Public Health, University of California at Los Angeles, CA, USA.
authors.forename: Beate
authors.initials: B
authors.lastname: Ritz
mesh_terms: D000393:Air Pollutants / Q000032:analysis* / Q000633:toxicity; D016022:Case-Control Studies; D003718:Denmark; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D040362:Geographic Information Systems; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009585:Nitrogen Dioxide / Q000032:analysis / Q000633:toxicity; D016017:Odds Ratio; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D052638:Particulate Matter / Q000032:analysis / Q000633:toxicity; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000393:Air Pollutants; D053583:Interleukin-1beta; D052638:Particulate Matter; D014409:Tumor Necrosis Factor-alpha; D009585:Nitrogen Dioxide
keywords: Gene-environment interaction; Inflammation; Parkinson's disease; Traffic-related air pollution