{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:41:57Z","timestamp":1791265317233,"version":"4.1.0"},"reference-count":44,"publisher":"American Chemical Society (ACS)","issue":"6","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":3232,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Research suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinson\u2019s disease (PD) risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials<\/jats:title>\n                    <jats:p>Methods: In 324 incident PD patients and 334 population controls from our rural California case\u2013control study, we genotyped rs2652510, rs2550956 (for the DAT 5\u2032 clades), and the 3\u2032 variable number of tandem repeats (VNTR). Using geographic information system methods, we determined residential exposure to agricultural maneb and paraquat applications. We also collected occupational pesticide use data. Employing logistic regression, we calculated odds ratios (ORs) for clade diplotypes, VNTR genotype, and number of susceptibility (A clade and 9-repeat) alleles and assessed susceptibility allele\u2013pesticide interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PD risk was increased separately in DAT A clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI), 1.08\u20132.57] and 3\u2032 VNTR 9\/9 carriers (9\/9 vs. 10\/10: OR = 1.8; 95% CI, 0.96\u20133.57), and our data suggest a gene dosing effect. Importantly, high exposure to paraquat and maneb in carriers of one susceptibility allele increased PD risk 3-fold (OR = 2.99; 95% CI, 0.88\u201310.2), and in carriers of two or more alleles more than 4-fold (OR = 4.53; 95% CI, 1.70\u201312.1). We obtained similar results for occupational pesticide measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Using two independent pesticide measures, we a) replicated previously reported gene\u2013environment interactions between DAT genetic variants and occupational pesticide exposure in men and b) overcame previous limitations of nonspecific pesticide measures and potential recall bias by employing state records and computer models to estimate residential pesticide exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1289\/ehp.0800277","type":"journal-article","created":{"date-parts":[[2009,2,21]],"date-time":"2009-02-21T22:37:29Z","timestamp":1235255849000},"page":"964-969","source":"Crossref","is-referenced-by-count":160,"title":["Dopamine Transporter Genetic Variants and Pesticides in Parkinson\u2019s Disease"],"prefix":"10.1021","volume":"117","author":[{"given":"Beate R.","family":"Ritz","sequence":"first","affiliation":[{"name":"Department of Epidemiology and"},{"name":"Department of Environmental Health Sciences, Center for Occupational and Environmental Health, UCLA School of Public Health, University of California at Los Angeles, Los Angeles, California, USA"},{"name":"Department of Neurology, UCLA School of Medicine, University of California at Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika D.","family":"Manthripragada","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadie","family":"Costello","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and"},{"name":"Department of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Lincoln","sequence":"additional","affiliation":[{"name":"Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Farrer","sequence":"additional","affiliation":[{"name":"Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myles","family":"Cockburn","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Bronstein","sequence":"additional","affiliation":[{"name":"Department of Neurology, UCLA School of Medicine, University of California at Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2009,2,22]]},"reference":[{"key":"2026080504063123400_micit1","volume-title":"The PDGene Database","author":"Bagade","year":"2008"},{"key":"2026080504063123400_micit2","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1289\/ehp.8095","article-title":"Pesticides and Parkinson\u2019s disease\u2014is there a link?","volume":"114","author":"Brown","year":"2006","journal-title":"Environ Health Perspect"},{"issue":"5","key":"2026080504063123400_micit3","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/BF01056333","article-title":"Occupational exposure and drift hazard during aerial application of paraquat to cotton","volume":"13","author":"Chester","year":"1984","journal-title":"Arch Environ Contam Toxicol"},{"key":"2026080504063123400_micit4","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1093\/aje\/kwp006","article-title":"Parkinson disease and residential exposure to maneb and paraquat from agricultural applications in the Central Valley of California","volume":"169","author":"Costello","year":"2009","journal-title":"Am Journal Epidemiol"},{"issue":"6","key":"2026080504063123400_micit5","first-page":"1062","article-title":"Drift residues of air-applied carbaryl in an orchard environment","volume":"75","author":"Currier","year":"1982","journal-title":"Entomology"},{"issue":"6","key":"2026080504063123400_micit6","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1002\/ana.20143","article-title":"Further evidence that interactions between CYP2D6 and pesticide exposure increase risk for Parkinson\u2019s disease","volume":"55","author":"Deng","year":"2004","journal-title":"Ann Neurol"},{"issue":"4\u20136","key":"2026080504063123400_micit7","first-page":"875","article-title":"Common human 5\u2032 dopamine transporter (SLC6A3) haplotypes yield varying expression levels in vivo","volume":"26","author":"Drgon","year":"2006","journal-title":"Cell Mol Neurobiol"},{"issue":"5","key":"2026080504063123400_micit8","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1002\/ana.410340504","article-title":"Neural degeneration and the transport of neurotransmitters","volume":"34","author":"Edwards","year":"1993","journal-title":"Ann Neurol"},{"issue":"3","key":"2026080504063123400_micit9","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/ana.20051","article-title":"CYP2D6 polymorphism, pesticide exposure, and Parkinson\u2019s disease","volume":"55","author":"Elbaz","year":"2004","journal-title":"Ann Neurol"},{"issue":"1\u20132","key":"2026080504063123400_micit10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jns.2007.06.024","article-title":"Epidemiologic studies of environmental exposures in Parkinson\u2019s disease","volume":"262","author":"Elbaz","year":"2007","journal-title":"J Neurol Sci"},{"issue":"3","key":"2026080504063123400_micit11","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1046\/j.1471-4159.1997.69031322.x","article-title":"Dopamine transporter is required for in vivo MPTP neurotoxicity: evidence from mice lacking the transporter","volume":"69","author":"Gainetdinov","year":"1997","journal-title":"J Neurochem"},{"issue":"6566","key":"2026080504063123400_micit12","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/379606a0","article-title":"Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter","volume":"379","author":"Giros","year":"1996","journal-title":"Nature"},{"key":"2026080504063123400_micit13","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/1476-072X-7-60","article-title":"An effective and efficient approach for manually improving geocoded data","volume":"7","author":"Goldberg","year":"2008","journal-title":"Int J Health Geogr"},{"key":"2026080504063123400_micit14","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/sj.mp.4001764","article-title":"Identification of additional variants within the human dopamine transporter gene provides further evidence for an association with bipolar disorder in two independent samples","volume":"11","author":"Greenwood","year":"2006","journal-title":"Molec Psychiat"},{"issue":"4","key":"2026080504063123400_micit15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s10048-008-0137-1","article-title":"Nitric oxide synthase genes and their interactions with environmental factors in Parkinson\u2019s disease","volume":"9","author":"Hancock","year":"2008","journal-title":"Neurogenetics"},{"issue":"7","key":"2026080504063123400_micit16","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1073\/pnas.82.7.2173","article-title":"Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity","volume":"82","author":"Javitch","year":"1985","journal-title":"Proc Natl Acad Sci USA"},{"issue":"9","key":"2026080504063123400_micit17","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1002\/mds.20513","article-title":"Clinical characteristics in early Parkinson\u2019s disease in a central California population-based study","volume":"20","author":"Kang","year":"2005","journal-title":"Mov Disord"},{"issue":"8","key":"2026080504063123400_micit18","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.envint.2005.04.001","article-title":"Air pollution and young children\u2019s inhalation exposure to organophosphorus pesticide in an agricultural community in Japan","volume":"31","author":"Kawahara","year":"2005","journal-title":"Environ Int"},{"issue":"20","key":"2026080504063123400_micit19","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1093\/hmg\/ddl247","article-title":"5\u2032 and 3\u2032 region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson\u2019s disease risk: a hypothesis-generating study","volume":"15","author":"Kelada","year":"2006","journal-title":"Hum Mol Genet"},{"key":"2026080504063123400_micit20","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1097\/01.fpc.0000170917.04275.d6","article-title":"Dopamine transporter (SLC6A3) 5\u2032 region haplotypes significantly affect transcriptional activity in vitro but are not associated with Parkinson\u2019s disease","volume":"15","author":"Kelada","year":"2005","journal-title":"Pharmacogenet Genomics"},{"issue":"2","key":"2026080504063123400_micit21","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/0006-8993(84)90777-7","article-title":"Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey","volume":"292","author":"Langston","year":"1984","journal-title":"Brain Res"},{"issue":"4","key":"2026080504063123400_micit22","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/1531-8249(200004)47:4<493::AID-ANA13>3.0.CO;2-4","article-title":"In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson\u2019s disease","volume":"47","author":"Lee","year":"2000","journal-title":"Ann Neurol"},{"key":"2026080504063123400_micit23","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1093\/jee\/79.2.459","article-title":"Drift comparisons between aerial and ground orchard application","volume":"79","author":"MacCollom","year":"1986","journal-title":"J Econ Entomol"},{"issue":"4","key":"2026080504063123400_micit24","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1097\/01.EDE.0000073160.79633.c1","article-title":"Geocoding addresses from a large population-based study: lessons learned","volume":"14","author":"McElroy","year":"2003","journal-title":"Epidemiology"},{"key":"2026080504063123400_micit25","unstructured":"National Center for Biotechnology Information\n          . 2009. UnigeneAvailable: http:\/\/www.ncbi.nlm.nih.gov\/unigene[accessed 24 April 2009]."},{"issue":"2","key":"2026080504063123400_micit26","doi-asserted-by":"crossref","first-page":"658","DOI":"10.2353\/ajpath.2007.060359","article-title":"Pesticide exposure exacerbates alpha-synucleinopathy in an A53T transgenic mouse model","volume":"170","author":"Norris","year":"2007","journal-title":"Am J Pathol"},{"key":"2026080504063123400_micit27","unstructured":"Oregon State University\n          . 1996a. Extension Toxicology Network: Pesticide Information Profiles: ManebAvailable: http:\/\/extoxnet.orst.edu\/pips\/maneb.htm[accessed 20 June 2008]."},{"key":"2026080504063123400_micit28","unstructured":"Oregon State University\n          . 1996b. Extension Toxicology Network: Pesticide Information Profiles: ParaquatAvailable: http:\/\/extoxnet.orst.edu\/pips\/paraquat.htm[accessed 20 June 2008]."},{"issue":"5\u20136","key":"2026080504063123400_micit29","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1089\/ars.2005.7.685","article-title":"Reactive oxygen and nitrogen species: weapons of neuronal destruction in models of Parkinson\u2019s disease","volume":"7","author":"Przedborski","year":"2005","journal-title":"Antioxid Redox Signal"},{"issue":"1","key":"2026080504063123400_micit30","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/toxsci\/kfi304","article-title":"Paraquat neurotoxicity is distinct from that of MPTP and rotenone","volume":"88","author":"Richardson","year":"2005","journal-title":"Toxicol Sci"},{"key":"2026080504063123400_micit31","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1196\/annals.1371.074","article-title":"Geographic model and biomarker-derived measures of pesticide exposure and Parkinson\u2019s disease","volume":"1076","author":"Ritz","year":"2006","journal-title":"Ann NY Acad Sci"},{"key":"2026080504063123400_micit32","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1289\/ehp.6118","article-title":"Historical pesticide exposure in California using pesticide use reports and land-use surveys: an assessment of misclassification error and bias","volume":"111","author":"Rull","year":"2003","journal-title":"Environ Health Perspect"},{"issue":"4","key":"2026080504063123400_micit33","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0168-0102(03)00163-9","article-title":"Paraquat leads to dopaminergic neural vulnerability in organotypic midbrain culture","volume":"46","author":"Shimizu","year":"2003","journal-title":"Neurosci Res"},{"issue":"3","key":"2026080504063123400_micit34","first-page":"289","article-title":"Changes in the function and ultra-structure of vessels in the rat model of multiple low dose streptozotocin-induced diabetes","volume":"25","author":"Sotnikova","year":"2006","journal-title":"Gen Physiol Biophys"},{"issue":"2","key":"2026080504063123400_micit35","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1369-1600.2007.00058.x","article-title":"Association between dopamine transporter genotypes and smoking cessation: a meta-analysis","volume":"12","author":"Stapleton","year":"2007","journal-title":"Adict Biol"},{"issue":"3","key":"2026080504063123400_micit36","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1046\/j.1460-9568.2003.02781.x","article-title":"Age-related irreversible progressive nigrostriatal dopaminergic neurotoxicity in the paraquat and maneb model of the Parkinson\u2019s disease phenotype","volume":"18","author":"Thiruchelvam","year":"2003","journal-title":"Eur J Neurosci"},{"issue":"24","key":"2026080504063123400_micit37","doi-asserted-by":"crossref","first-page":"9207","DOI":"10.1523\/JNEUROSCI.20-24-09207.2000","article-title":"The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson\u2019s disease","volume":"20","author":"Thiruchelvam","year":"2000","journal-title":"J Neurosci"},{"issue":"suppl 7","key":"2026080504063123400_micit38","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1002\/mds.10578","article-title":"Dopamine transporter: basic science and human variation of a key molecule for dopaminergic function, locomotion, and parkinsonism","volume":"18","author":"Uhl","year":"2003","journal-title":"Mov Disord"},{"key":"2026080504063123400_micit39","unstructured":"U.S EPA\n          . 2005. Reregistration Eligibility Decision (RED) for Maneb Availablehttp:\/\/www.epa.gov\/oppsrrd1\/REDs\/maneb_red.pdf[accessed 20 June 2008]."},{"issue":"1\u20132","key":"2026080504063123400_micit40","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0169-328X(92)90165-8","article-title":"A human dopamine transporter cDNA predicts reduced glycosylation, displays a novel repetitive element and provides racially-dimorphic TaqI RFLPs","volume":"15","author":"Vandenbergh","year":"1992","journal-title":"Brain Res Mol Brain Res"},{"issue":"1","key":"2026080504063123400_micit41","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.nbd.2006.02.012","article-title":"Inhibitory effects of pesticides on proteasome activity: implication in Parkinson\u2019s disease","volume":"23","author":"Wang","year":"2006","journal-title":"Neurobiol Dis"},{"issue":"4","key":"2026080504063123400_micit42","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/ajmg.b.30453","article-title":"A meta-analysis of association studies between 10-repeat allele of a VNTR polymorphism in the 3\u2032-UTR of dopamine transporter gene and attention deficit hyperactivity disorder","volume":"144B","author":"Yang","year":"2007","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"issue":"11","key":"2026080504063123400_micit43","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1136\/oem.2003.011742","article-title":"Use of a crop and job specific exposure matrix for estimating cumulative exposure to triazine herbicides among females in a case-control study in the Central Valley of California","volume":"61","author":"Young","year":"2004","journal-title":"Occup Environ Med"},{"issue":"2","key":"2026080504063123400_micit44","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.neuroscience.2004.06.048","article-title":"Proteasomal inhibition induced by manganese ethylene-bis-dithiocarbamate: relevance to Parkinson\u2019s disease","volume":"128","author":"Zhou","year":"2004","journal-title":"Neuroscience"}],"container-title":["Environmental Health Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/117\/6\/964\/66400240\/ehp.0800277.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/117\/6\/964\/66400240\/ehp.0800277.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:46:41Z","timestamp":1786628801000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-lookup\/doi\/10.1289\/ehp.0800277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2,22]]},"references-count":44,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2009,2,22]]},"published-print":{"date-parts":[[2009,6,1]]}},"URL":"https:\/\/doi.org\/10.1289\/ehp.0800277","relation":{},"ISSN":["0091-6765","1552-9924"],"issn-type":[{"value":"0091-6765","type":"print"},{"value":"1552-9924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,2,22]]}}}