Details

Autor(en) / Beteiligte

• Ritz, Beate R
• Manthripragada, Angelika D
• Costello, Sadie
• Lincoln, Sarah J
• Farrer, Matthew J
• Cockburn, Myles
• Bronstein, Jeff

Titel

Dopamine Transporter Genetic Variants and Pesticides in Parkinsonas Disease

Ist Teil von

• Environmental health perspectives, 2009-06, Vol.117 (6), p.964-969

Erscheinungsjahr

2009

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Background Research suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinsonas disease (PD) risk. Materials Methods: In 324 incident PD patients and 334 population controls from our rural California caseacontrol study, we genotyped rs2652510, rs2550956 (for the DAT 5a2 clades), and the 3a2 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 alleleapesticide interactions. Results PD risk was increased separately in DAT A clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI), 1.08a2.57] and 3a2 VNTR 9/9 carriers (9/9 vs. 10/10: OR = 1.8; 95% CI, 0.96a3.57), 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, 0.88a10.2), and in carriers of two or more alleles more than 4-fold (OR = 4.53; 95% CI, 1.70a12.1). We obtained similar results for occupational pesticide measures. Discussion Using two independent pesticide measures, we a) replicated previously reported geneaenvironment 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. Conclusion Our results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk.