Paraoxonase 1 Met-Leu 54 polymorphism is associated with Parkinson's disease

Two up-to-date known paraoxonase 1 (PON1) polymorphisms (GIn-Arg 191 and Le u-Met 54) affect the hydrolysis of toxic oxons and might intensify effects of pollutants, organophosphates and other environmental chemicals in develo pment of Parkinson's disease (PD). We reported previously that PON1 Gln-Arg 191 polymorphism did not influence on the susceptibility to PD. In the pre sent study we have investigated the PON1 Leu-Met 54 polymorphism in 117 pat ients with sporadic idiopathic PD. A new approach for Leu-Met 54 polymorphi sm genotyping has been developed. We have showed the frequency of the Met 5 4 allele of PON1 to be significantly increased in patients with PD compared with the controls (chi (2)=8.63, df=1, P<0.003). The relative risk of PD i n the Met 54 allele carriers has been estimated to be 2.3 fold higher than in homozygotes for the L allele. Moreover it appeared to be even 5.15 highe r in the subgroup of patients with early-onset PD. We suggest that the Met 54 allele may be considered to be an independent risk factor for PD. This m utation could probably cause PON1 impaired metabolism of environmental neur otoxins and might be responsible for neurodegeneration. <(c)> 2001 Publishe d by Elsevier Science B.V.