The Relativity Study On The Genetic Polymorphism Of Detoxifing Enzymes And Hereditary Susceptibility Of Parkinson's Disease

Parkinson's Disease (PD) , a common neurodegenerative disorder in central nervous system among the middle and the old. Its pathological hallmark is selective degeneration and prominent loss of dopaminergic neurons in the pars compacta substantia nigra. The etiology and pathogenesis of PD is still unclear. More and more research results demonstrated that PD is caused by the interaction between genetic and environmental factors. When there is a defect of detoxifing enzymes system, it can induce the accumulation of environmental toxins in the body and subsequently the toxins damage the neurons in substantia nigra chronically. The xenobiotic metabolism is complex and depends on the interaction and active balance of many kinds of detoxifing enzymes. Phase I enzyme cytochrome P450 (CYP1A1) and phase II enzyme N-acetyltransferase 2 (NAT2) are main enzymes which involve in the metabolism of xenobiotic. They were found to be distributed differently in different race, and their activity is obvious different in different individuals. Its polymorphisms are controlled by genetic factors. As a result, their polymorphisms might be associated with hereditary susceptibility of PD. To investigate whether the Mspl polymorphism of CYP1A1 and the genetic polymorphism of N-acetyltransferase 2 (NAT2) gene are associated with the hereditary susceptibility of early-onset idiopathic PD, and to analyze the synergy between Mspl polymorphisms of CYP1A1 gene and slow acetylator genotype of NAT2 gene in the early-onsetidiopathic PD. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), three genotypes A,B and C in 3'-flanking region of CYP1A1 and slow acetylator genotype of NAT2 were studied in 126 patients with early-onset idiopathic PD and 122 age-matched randomly selected controls. The differences of the frequencies of genotypes A,B and C were not statistically significant in two groups; The frequency of slow acetylator genotype was higher in the patients (23.0%) than in the controls (10.7%), with an OR of 2.507 ; the combining analysis of the polymorphisms showed significant higher frequencies of the co-existance of Mspl B and slow acetylator genotype in the patients (62.1%). with an OR of 5.455. Our results suggest that the Mspl polymorphisms of CYP1 Al itself might not be association with early-onset idiopathic PD, but the slow acetylator genotype of N-acetyltransferase 2 might be associated with an increased risk for idiopathic early-onset PD, and there may be a synergy between Mspl B of CYP1A1 and slow acetylator genotype of NAT2 on the increased risk of PD.