A case-control study of Parkinson's disease and tobacco use: Gene-tobacco interactions

Abstract

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.

Exposure to pesticides and heterozygote genotype of GSTP1-Alw26I are associated to Parkinson's disease

“…However, given the numerous candidate gene studies in different cases, genetic markers showing disequilibrium are scarce, which allows investigators to ignore the distribution of genotypes suggesting disequilibrium, therefore ignoring valuable information to identify casual polymorphisms 23 . The polymorphism GSTP1-Alw26I, when related to tobacco use and alcoholism, was the same in the SG, SSG and CG groups, as well as in other studies involving smoking and PD 10,22,25 . On the other hand, there are references of tobacco protection in PD, including haplotypes of GSTP1…”

“…Exposure to pesticides consisted of any previous occupational exposure to such products, despite its duration 8 . Tobacco use included constant smoking of cigarettes, daily and continuously, for more than six months 10 . Alcoholism included the consumption of at least 40 g of alcohol per day 19 .…”

“…The catalytic efficiency of the GSTP1 variants differs from that of the wild type, and it varies according to the characteristics of the substrates, manly distinct 26 . This explains the protective effect of the mutant allele regarding diol epoxides found in tobacco products 10 , in contrast with its reduced effects upon detoxification of pesticides 7 . In this study, there was an association between smoking and wild homozygote genotype in familial PD patients, confirming the studies by Pal et al 26 and De Palma et al 10 .…”

“…Also, GSTP1 polymorphisms can influence onset age for PD 4,9 . On the other hand, there are controversies surrounding the risks or protection, involving GSTP1, tobacco use and PD 10 . GSTP1 polymorphisms have been first described by Board et al 11 Following studies demonstrated important allelic differences in substrate selectivity, which usually reduces GSTP1 activity 7,12 .…”

Original article Association of monoamine oxidase B and catechol-O-methyltransferase polymorphisms with sporadic Parkinson’s disease in an Iranian population

“…On the contrary, a significant association between the G allele of MAOB and an increased PD risk was observed [6,33,39]. Other studies found no association between this polymorphism and the PD risk in Asian, Caucasian, Australian, Polish, British populations, and five other European countries (Italy, Malta, Romania, Scotland, and Sweden) [2,9,13,14,27,38]. Since the MAOB gene is located on the X chromosome; the distribution of the alleles was also evaluated in both sexes.…”