GSTM1 and mEPHX polymorphisms in Parkinson's disease and age of onset

Both environmental and genetic factors are involved in the development of P D and biotransformation of exogenous and endogenous compounds and may play a role in inter-individual susceptibility. Therefore, we investigated the p resence of null genotypes of GSTM1, GSTT1, and two polymorphisms of mEPHX i n subjects with Parkinson's disease and in a reference population. The stud y included 35 male PD patients and a male control group including 283 subje cts. Homozygosity of the histidine (H) 113 isoform of mEPHX was significant ly increased in PD patients (odds ratio = 3.8 CI 95% 1.2-11.8) and analysis of allele frequencies displayed an increased frequency of the H-allele amo ng PD patients (odds ratio = 1.9 CI 95% 1.1-3.3), However, a significantly elevated median age for the onset of PD was found among GSTM1 gene carriers (median age = 68 years) compared to PD patients being GSTM1 null genotypes (median age = 57 years). Our observations suggest that (H) 113 isoform of mEPHX, which has been suggested as a low activity isoform, is overrepresent ed in PD patients and that inherited carriers of the GSTM1 gene postpone th e onset of PD. These detoxification pathways may represent important protec tive mechanisms against reactive intermediates modifying the susceptibility and onset of PD. (C) 2000 Academic Press.