Free Access
Neuroepidemiology 2010;35:191–195
(DOI:10.1159/000315157)

α-Synuclein Gene May Interact with Environmental Factors in Increasing Risk of Parkinson’s Disease

Gatto N.M.a · Rhodes S.L.a · Manthripragada A.D.a · Bronstein J.c · Cockburn M.d · Farrer M.e · Ritz B.a–c
Departments of aEpidemiology, bEnvironmental Health Sciences and cNeurology, University of California Los Angeles, and dDepartment of Preventive Medicine, University of Southern California, Los Angeles, Calif., USA, and eDepartment of Medical Genetics, University of British Columbia, Vancouver, B.C., Canada
email Corresponding Author


 goto top of outline Key Words

  • α-Synuclein
  • Pesticides
  • Parkinson’s disease
  • Smoking
  • Age of onset
  • Paraquat
  • Interaction
  • REP1

 goto top of outline Abstract

Background: Although of great interest and suggested in prior reports, possible α-synuclein (SNCA) gene-environment interactions have not been well investigated in humans. Methods: We used a population-based approach to examine whether the risk of Parkinson’s disease (PD) depended on the combined presence of SNCA variations and two important environmental factors, pesticide exposures and smoking. Results/Conclusions: Similar to recent meta- and pooled analyses, our data suggest a lower PD risk in subjects who were either homozygous or heterozygous for the SNCA REP1 259 genotype, and a higher risk in subjects who were either homozygous or heterozygous for the REP1 263 genotype, especially among subjects with an age of onset ≤68 years. More importantly, while analyses of interactions were limited by small cell sizes, risk due to SNCA variations seemed to vary with pesticide exposure and smoking, especially in younger onset cases, suggesting an age-of-onset effect.

Copyright © 2010 S. Karger AG, Basel


 goto top of outline References
  1. Lashuel HA, Petre BM, Wall J, Simon M, Nowak RJ, Walz T, Lansbury PT Jr: Alpha-synuclein, especially the Parkinson’s disease-associated mutants, forms pore-like annular and tubular protofibrils. J Mol Biol 2002;322:1089–1102.
  2. Nishioka K, Hayashi S, Farrer MJ, Singleton AB, Yoshino H, Imai H, Kitami T, Sato K, Kuroda R, Tomiyama H, Mizoguchi K, Murata M, Toda T, Imoto I, Inazawa J, Mizuno Y, Hattori N: Clinical heterogeneity of alpha-synuclein gene duplication in Parkinson’s disease. Ann Neurol 2006;59:298–309.
  3. Chiba-Falek O, Touchman JW, Nussbaum RL: Functional analysis of intra-allelic variation at NACP-Rep1 in the alpha-synuclein gene. Hum Genet 2003;113:426–431.
  4. Pals P, Lincoln S, Manning J, Heckman M, Skipper L, Hulihan M, Van den Broeck M, De Pooter T, Cras P, Crook J, Van Broeckhoven C, Farrer MJ: alpha-Synuclein promoter confers susceptibility to Parkinson’s disease. Ann Neurol 2004;56:591–595.
  5. Kay DM, Factor SA, Samii A, Higgins DS, Griffith A, Roberts JW, Leis BC, Nutt JG, Montimurro JS, Keefe RG, Atkins AJ, Yearout D, Zabetian CP, Payami H: Genetic association between alpha-synuclein and idiopathic Parkinson’s disease. Am J Med Genet B Neuropsychiatr Genet 2008;147B: 1222–1230.
  6. Maraganore DM, de Andrade M, Elbaz A, Farrer MJ, Ioannidis JP, Krüger R, Rocca WA, Schneider NK, Lesnick TG, Lincoln SJ, Hulihan MM, Aasly JO, Ashizawa T, Chartier-Harlin MC, Checkoway H, Ferrarese C, Hadjigeorgiou G, Hattori N, Kawakami H, Lambert JC, Lynch T, Mellick GD, Papapetropoulos S, Parsian A, Quattrone A, Riess O, Tan EK, Van Broeckhoven C, Genetic Epidemiology of Parkinson’s Disease (GEO-PD) Consortium: Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease. JAMA 2006;296:661–670.
  7. Priyadarshi A, Khuder SA, Schaub EA, Priyadarshi SS: Environmental risk factors and Parkinson’s disease: a metaanalysis. Environ Res 2001;86:122–127.
  8. Costello S, Cockburn M, Bronstein J, Zhang X, Ritz B: Parkinson’s disease and residential exposure to maneb and paraquat from agricultural applications in the central valley of California. Am J Epidemiol 2009;169:919–926.
  9. Gatto NM, Cockburn M, Bronstein J, Manthripragada AD, Ritz B: Well-water consumption and Parkinson’s disease in rural California. Environ Health Perspect 2009;117:1912–1918.
  10. Ritz BR, Manthripragada AD, Costello S, Lincoln SJ, Farrer MJ, Cockburn M, Bronstein J: Dopamine transporter genetic variants and pesticides in Parkinson’s disease. Environ Health Perspect 2009;117:964–969.
  11. Fernagut PO, Hutson CB, Fleming SM, Tetreaut NA, Salcedo J, Masliah E, Chesselet MF: Behavioral and histopathological consequences of paraquat intoxication in mice: effects of alpha-synuclein over-expression. Synapse 2007;61:991–1001.
  12. Norris EH, Uryu K, Leight S, Giasson BI, Trojanowski JQ, Lee VM: Pesticide exposure exacerbates alpha-synucleinopathy in an A53T transgenic mouse model. Am J Pathol 2007;170:658–666.
  13. Brighina L, Frigerio R, Schneider NK, Lesnick TG, de Andrade M, Cunningham JM, Farrer MJ, Lincoln SJ, Checkoway H, Rocca WA, Maraganore DM: Alpha-synuclein, pesticides, and Parkinson disease: a case-control study. Neurology 2008;70:1461–1469.
  14. McCulloch CC, Kay DM, Factor SA, Samii A, Nutt JG, Higgins DS, Griffith A, Roberts JW, Leis BC, Montimurro JS, Zabetian CP, Payami H: Exploring gene-environment interactions in Parkinson’s disease. Hum Genet 2008;123:257–265.
  15. Kang GA, Bronstein JM, Masterman DL, Redelings M, Crum JA, Ritz B: Clinical characteristics in early Parkinson’s disease in a central California population-based study. Mov Disord 2005;20:1133–1142.
  16. Ritz B, Costello S: Geographic model and biomarker-derived measures of pesticide exposure and Parkinson’s disease. Ann NY Acad Sci 2006;1076:378–387.
  17. Goldberg DW, Zhang X, Marusek JC, Wilson JP, Ritz B, Cockburn MG: Development of an automated pesticide exposure analyst for the California’s Central Valley. Proc Urban Regional Info Syst Assoc GIS Public Health Conf, New Orleans, 2007.
  18. Rull RP, Ritz B: Historical pesticide exposure in California using pesticide use reports and land-use surveys: an assessment of misclassification error and bias. Environ Health Perspect 2003;111:1582–1589.

 goto top of outline Author Contacts

Prof. Beate Ritz, MD, PhD
Schools of Public Health and Medicine, UCLA
650 Charles E. Young Drive, Box 951772
Los Angeles, CA 90095 1772 (USA)
Tel. +1 310 206 7458, Fax +1 310 206 6039, E-Mail britz@ucla.edu


 goto top of outline Article Information

Received: March 25, 2010
Accepted: May 11, 2010
Published online: July 24, 2010
Number of Print Pages : 5
Number of Figures : 0, Number of Tables : 2, Number of References : 18


 goto top of outline Publication Details

Neuroepidemiology

Vol. 35, No. 3, Year 2010 (Cover Date: October 2010)

Journal Editor: Feigin V.L. (Auckland)
ISSN: 0251-5350 (Print), eISSN: 1423-0208 (Online)

For additional information: http://www.karger.com/NED


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