The Association Analysis Of COMT Genetic Polymorphisms With The Susceptibility Of Parkinson’s Disease And Levodopa Induced Dysikinesia

Objectives:The aims of this study were to explore the distributive characteristics of the most common COMT gene mutations and haplotypes (rs6269A>G, rs4633C>T, rs4818C>G and rs4680A>G) in Chinese Parkinson’s disease patients and health control subjects, and investigate whether these mutations and haplotypes affect the PD risk and anti-parkinsonian drugs levodopa induced dysikinesia in PD patients.Methods:The genotypes of rs6269and rs4633ware determined by PCR-RFLP method and the genotypes of rs4818and rs4680ware determined by direct sequencing assay in188Parkinson’s disease patients and111healthy volunteers. Patients as classified into two groups depending on the presence or absence of anti-parkinsonian drugs levodopa-induced dyskinesias (LID).Results:The frequency of A-T-C-A/A-T-C-A (M/M) haplotype carriers was lower in early-onset PD (EOPD) patients compared with controls with borderline significance (P=0.050), may reduce the risk of EOPD occurred (adjusted OR=0.062). Of the188examined PD patients,22exhibited LID and166did not. Rs4633CT, CC or CC+CT genotype carriers decreased risk of LID, after adjusting the potential confounders OR=0.131,0.106,0.118, respective. Rs4680GA、GG or GG+GA genotype carriers also decreased risk of LID, after adjusting the potential confounders OR=0.110,0.123,0.118, respective. The frequency of G-C-G-G(H), A-T-C-A(M), A-C-C-G(L) and A-T-C-G haplotypes were over0.01. The frequencies of M/M haplotype was significantly higher in dyskinesia than those in the non-dyskinesia controls (3.0%vs13.6%), after adjusting the potential confounders P=0.046, OR=9.433. We did not find any significant differences in other individual SNPs and haplotypes frequencies between PD, EOPD, LOPD cases and healthy volunteer controls or dyskinesia and non-dyskinesia controls.Conclusions:M/M haplotype carriers increased risk of LID and may reduce the risk of EOPD. Rs4633CT, CC or CC+CT and rs4680GA、GG or GG+GA genotype carriers decreased risk of LID. In our study, other individual SNPs and haplotypes of the COMT were no associated with the susceptibility of PD and LID.