RT Journal Article
SR Electronic
T1 Gene-environment interactions in parkinsonism and Parkinson’s disease: the Geoparkinson study
JF Occupational and Environmental Medicine
JO Occup Environ Med
FD BMJ Publishing Group Ltd
SP 673
OP 680
DO 10.1136/oem.2006.032078
VO 64
IS 10
A1 F D Dick
A1 G De Palma
A1 A Ahmadi
A1 A Osborne
A1 N W Scott
A1 G J Prescott
A1 J Bennett
A1 S Semple
A1 S Dick
A1 P Mozzoni
A1 N Haites
A1 S Bezzina Wettinger
A1 A Mutti
A1 M Otelea
A1 A Seaton
A1 P Soderkvist
A1 A Felice
YR 2007
UL http://oem.bmj.com/content/64/10/673.abstract
AB Objectives: To investigate associations of Parkinson’s disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk.Methods: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders.Results: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% CI 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only).Conclusions: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.