Genetic polymorphisms of microsomal and soluble epoxide hydrolase and the risk of Parkinson's disease

Oxidative stress is hypothesized to play a major role in the destruction of dopaminergic neurons, which is associated with Parkinson's disease. Epoxid es are potentially reactive intermediates formed through the oxidative meta bolism of both exogenous and endogenous substances that contribute to cytot oxic damage mediated by oxidative stress. The microsomal (EPHX1) and solubl e (EPHX2) epoxide hydrolases function to regulate the oxidation status of a wide range of xenobiotic- and lipid-derived substrates; therefore, interin dividual variation in these pathways may mitigate epoxide-related cellular injury. In this investigation, we examined the potential association betwee n the risk of Parkinson's disease and genetic variation within the EPHX1 an d EPHX2 genes. Fluorescent 5' nuclease-based assays were developed to ident ify the allelic status of individuals with respect to specific single nucle otide polymorphisms in exons 3 and 4 of the EPHX1 gene and exons 8 and 13 o f the EPHX2 gene. EPHX1 and EPHX2 genotype data were obtained from 133 idio pathic Parkinson's disease patients and 212 control subjects matched on age , gender and ethnicity. No statistically significant differences were found in the distribution of the reference and variant alleles between Parkinson 's disease and control subjects, or when results were stratified by gender. Therefore, common polymorphisms within EPHX1 and EPHX2 do not appear to be important risk factors for Parkinson's disease. Pharmacogenetics 11:703-70 8 (C) 2001 Lippincott Williams & Wilkins.