A case-control study of Parkinson's disease and tobacco use: gene-tobacco interactions.
A case-control study of genetic, environmental, and occupational risk factors for Parkinson's disease (PD) was carried out in five European countries (Italy, Malta, Romania, Scotland, and Sweden) to explore the possible contribution of interactions among host and environmental factors in sporadic PD. Whereas smoking habits confirmed its negative association with PD, a possible modulatory role of genetic polymorphisms was investigated to obtain further mechanistic insights. We recruited 767 cases of PD and 1989 age-matched and gender-matched controls. Participants completed an interviewer-administered questionnaire including the history of smoking habits. The polymorphisms of genes involved either in metabolism of compounds contained in tobacco smoke (CYP2D6, CYP1B1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, SOD2, EPHX and NAT2) or in dopaminergic neurotransmission (MAOA, MAOB, DAT1 and DRD2) were characterized by PCR based methods on genomic DNA. We found evidence of statistically significant gene-tobacco interaction for GSTM1, NAT2, and GSTP1, the negative association between tobacco smoking and PD being significantly enhanced in subjects expressing GSTM1-1 activity, in NAT2 fast acetylators, and in those with the GSTP1*B*C haplotype. Owing to the retrospective design of the study, these results require confirmation.
De Palma
Giuseppe
G
Department of Experimental and Applied Medicine, University of Brescia, Italy. depalma@med.unibs.it
Dick
Finlay D
FD
Calzetti
Stefano
S
Scott
Neil W
NW
Prescott
Gordon J
GJ
Osborne
Aileen
A
Haites
Neva
N
Mozzoni
Paola
P
Negrotti
Anna
A
Scaglioni
Augusto
A
Mutti
Antonio
A
D000368:Aged; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects; D010300:Parkinson Disease / Q000453:epidemiology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D014029:Tobacco Use Disorder / Q000453:epidemiology* / Q000235:genetics*