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. DESIGN: Case-control study. SETTING: Mutualité Sociale Agricole. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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.
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. DESIGN: Case-control study. SETTING: Mutualité Sociale Agricole. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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.
Authors: Shannon L Rhodes; Daniel D Buchanan; Ismaïl Ahmed; Kent D Taylor; Marie-Anne Loriot; Janet S Sinsheimer; Jeff M Bronstein; Alexis Elbaz; George D Mellick; Jerome I Rotter; Beate Ritz Journal: Neurobiol Dis Date: 2013-10-08 Impact factor: 5.996
Authors: Sarah E Lacher; Julia N Gremaud; Kasse Skagen; Emily Steed; Rachel Dalton; Kent D Sugden; Fernando Cardozo-Pelaez; Catherine M T Sherwin; Erica L Woodahl Journal: J Pharmacol Exp Ther Date: 2013-12-02 Impact factor: 4.030
Authors: Shannon L Rhodes; Arthur G Fitzmaurice; Myles Cockburn; Jeff M Bronstein; Janet S Sinsheimer; Beate Ritz Journal: Environ Res Date: 2013-08-27 Impact factor: 6.498