Enviironmental and Genetic Determinants of Parkinsonism from a Case-Control Study in Brescia, Italy

Abstract

INTRODUCTION. Environmental exposure to metals, solvents and pesticides has been shown consistently to play a role in the genesis of Parkinson’s disorders (PD) when interacting with genetic predisposition. We addressed the risk of developing PD from occupational and environmental exposure to neurotoxicants and polymorphisms of genes involved in metal transportation (ATP13A2, DMT1, SLC30A10) or neurodegeneration (ɑ Synuclein, SNCA). METHODS. A hospital-based case-control study was conducted in the highly industrialized province of Brescia, Italy. A total of 432 PD patients (38% females) were frequency-matched on age and hospital admission with 444 controls with no known neurological disease. Direct interview provided information on lifetime environmental and occupational exposure, tobacco smoking, dietary habits. Job titles and industrial activities were blindly coded following international criteria. Genotyping was assessed by PCR-RFLP. Odds ratio and 95% confidence intervals were calculated from unconditional logistic regression, adjusted for gender, age, education, smoking. Hardy-Weinberg equilibrium was tested for each of the polymorphisms investigated. RESULTS. A statistically significant increased risk of PD was observed among subjects having at least one parent affected by PD or tremors, carriers of homozygous recessive allele of SNCA rs356219 (OR 1.79, 95% CI 1.19 to 2.7), workers exposed to metals (OR 2,25, 95% CI 1.26 to 4.02), males occupied as metal working machine tool setters and operators (OR 2.15, p 0.04). The selection and recall bias that could affect the results appear to be balanced by the large sample size and the experience of direct interviewers. CONCLUSION. These data confirm and further support the hypothesis of environmental and genetic factors as determinants of PD. The role of metal exposure was especially outlined by this study that was conducted in a highly industrialized region.