Dopamine transporter genetic variants and pesticides in Parkinson's disease.
BACKGROUND
Research suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinson's disease (PD) risk.


METHODS



METHODS
In 324 incident PD patients and 334 population controls from our rural California case-control study, we genotyped rs2652510, rs2550956 (for the DAT 5' clades), and the 3' 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-pesticide interactions.


RESULTS
PD risk was increased separately in DAT A clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI), 1.08-2.57] and 3' VNTR 9/9 carriers (9/9 vs. 10/10: OR = 1.8; 95% CI, 0.96-3.57), 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, 0.88-10.2), and in carriers of two or more alleles more than 4-fold (OR = 4.53; 95% CI, 1.70-12.1). We obtained similar results for occupational pesticide measures.


CONCLUSIONS
Using two independent pesticide measures, we a) replicated previously reported gene-environment 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.


CONCLUSIONS
Our results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk.
Ritz
Beate R
BR
Department of Epidemiology, Center for Occupational and Environmental Health, UCLA School of Public Health, University of California at Los Angeles, Los Angeles, California 90095-1772, USA. britz@ucla.edu
Manthripragada
Angelika D
AD
Costello
Sadie
S
Lincoln
Sarah J
SJ
Farrer
Matthew J
MJ
Cockburn
Myles
M
Bronstein
Jeff
J
D016022:Case-Control Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008344:Maneb / Q000633:toxicity; D008875:Middle Aged; D010269:Paraquat / Q000633:toxicity; D010300:Parkinson Disease / Q000235:genetics*; D010575:Pesticides / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
D050483:Dopamine Plasma Membrane Transport Proteins; D004785:Environmental Pollutants; D010575:Pesticides; D008344:Maneb; D010269:Paraquat