Association between a promoter polymorphism of the paraoxonase PON1 gene and pathologically verified idiopathic Parkinson's disease

Background:  Exposure to pesticide is associated with an elevated risk of Parkinson’s disease (PD). Oxidative stress is also implicated in the etiology of PD. Paraoxonase (PON1) detoxifies organophosphates and exhibits antioxidant properties. It was postulated that polymorphisms of the PON1 gene lead to increased risk of PD. Methods:  The seven polymorphisms of the PON1 gene were typed and neuropathologic examination performed in 360 Japanese people (191 men and 169 women) consecutively autopsied at a general hospital. Results:  Thirty-three patients (18 men and 15 women) were diagnosed with pathologically verified idiopathic PD (pviPD). The proportion of male patients with pviPD was highest in the AA genotype (29.4%) of the G(−824)A polymorphism, followed by the GA genotype (9.3%), and least in the GG genotype (6.0%). These genotypic distributions and allele frequency were significantly different between male patients with and without pviPD (P = 0.021 and P = 0.012, respectively). The odds ratio for the −824 A allele versus the −824G allele was 2.47 (95% CI 1.23–4.96). No association between pviPD and the PON1 polymorphisms was found in the female patients. Conclusion:  Possession of the −824A allele may increase the risk of PD in Japanese men.