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.