Interaction between ABCB1 and professional exposure to organochlorine insecticides in Parkinson disease.
OBJECTIVE
To study the association between Parkinson disease (PD) and 2 polymorphisms in ABCB1 among subjects enrolled in the French health system for agricultural workers (Mutualité Sociale Agricole), as well as the interaction between ABCB1 and organochlorine insecticides.


METHODS
Case-control study.


METHODS
Mutualité Sociale Agricole.


METHODS
Patients with PD were examined by a neurologist and were matched to a maximum of 3 controls. Participants were classified as never users, users for gardening, and professional users of pesticides. Detailed information on pesticides lifelong use was obtained for professional users by occupational health physicians.


METHODS
DNA was obtained and 2 ABCB1 polymorphisms (exon 21: G2677[A,T]; exon 26: C3435T) associated with altered P-glycoprotein function were genotyped.


RESULTS
Among 207 cases and 482 matched controls, ABCB1 polymorphisms were not associated with PD (C3435T, P = .43; G2677[A,T], P = .97). Among 101 male cases and 234 matched controls, the odds ratio for organochlorines was 3.5 (95% confidence interval, 0.9-14.5) times higher among homozygous carriers of variant G2677(A,T) alleles than noncarriers. Among cases only, we found an association between carrying 2 variant G2677(A,T) alleles and organochlorines (odds ratio, 5.4, 95% confidence interval, 1.1-27.5) as well as with the number of cumulative lifetime number of hours of exposure (P = .005; analyses restricted to subjects exposed to organochlorines, P = .03).


CONCLUSIONS
Our findings suggest that the ABCB1 gene and exposure to organochlorine insecticides interact to increase PD risk: in subjects professionally exposed to organochlorines, polymorphisms associated with a decreased ability of ABCB1 to clear xenobiotics from the brain increased the risk of PD. These findings support the hypothesis of gene x pesticides interactions in PD.
Dutheil
Fabien
F
INSERM UMR-S775, Bases Moléculaires de la Réponse aux Xénobiotiques, Université Paris Descartes, Paris, France.
Beaune
Philippe
P
Tzourio
Christophe
C
Loriot
Marie-Anne
MA
Elbaz
Alexis
A
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016001:Confidence Intervals; D005091:Exons / Q000235:genetics; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects* / Q000706:statistics & numerical data; D010300:Parkinson Disease / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D010575:Pesticides / Q000633:toxicity*; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D010575:Pesticides