COMT基因多态性与帕金森病易感性及左旋多巴诱导异动症的相关性研究

发布时间：2018-03-29 07:56

本文选题：帕金森病　切入点：COMT　出处：《中南大学》2014年硕士论文

【摘要】：目的：研究COMT基因rs6269, rs4633, rs4818和rs4680多态性及其构成的单倍型与帕金森病的易患性及左旋多巴诱导的异动症的相关性。方法：rs6269和rs4633采用PCR-RFLP方法,rs4818和rs4680采用直接测序法对188名帕金森病患者和111名健康对照者进行基因分型。患者根据是否出现左旋多巴诱导的异动症分为非异动组和异动组。结果：在早发帕金森病组中,A-T-C-A/A-T-C-A (M/M)型患者的分布频率比对照组低,具有边缘统计学意义(P=0.050),可能减少早发帕金森病发生的风险(校正后OR=0.062)。最终入组的188例患者中,有22例出现了左旋多巴诱导的异动症。rs4633CT、CC或者CC+CT基因型携带者出现异动症不良反应的风险明显降低,校正后OR分别为0.131、0.106、0.118。rs4680GA、GG或者GG+GA基因型携带者出现异动症不良反应的风险也明显降低,校正后OR分别为0.110、0.123、0.118。单倍型分析中发现G-C-G-G(H)、 A-T-C-A(M).A-C-C-G(L)及A-T-C-G共4个频率大于0.01的单倍型,M/M单倍体基因型在非异动组和异动组的分布频率分别为(3.0%vs13.6%),经校正后P=0.046,OR=9.433在异动和非异动组的分布具有统计学差异。COMT其他的基因多态性位点及其构成的单倍型在健康受试者和PD、EOPD、LOPD患者之间,非异动和异动组之间的分布均没有显著性差异。结论：COMT中M/M单倍体基因型携带者有减少早发型PD发生风险的趋势,但出现异动症的风险则明显增加。rs4633CT、CC或者CC+CT基因型,rs4680GA、GG或者GG+GA基因型携带者出现异动症的风险明显降低；COMT中其他基因多态性位点及其构成的单倍型则与中国汉族人群中散发性帕金森病患者的疾病易感性和左旋多巴诱导的异动症的发生没有明显相关性。
[Abstract]:Objective: to study the association of polymorphisms of COMT genes rs6269, rs4633, rs4818 and rs4680 and their haplotypes with susceptibility to Parkinson's disease and levodopa-induced dyskinesia. Methods Genomic typing was carried out in 188 Parkinson's disease patients and 111 healthy controls by PCR-RFLP, rs4818 and rs4680, respectively. According to the presence or absence of levodopa-induced dyskinesia, the patients were divided into two groups. Results: the distribution frequency of A-T-C-A / A-T-C-A / M / M / M type in early onset Parkinson's disease group was lower than that in the control group, and had marginal statistical significance (P < 0.050), which may reduce the risk of early onset Parkinson's disease (corrected OR0.062). In 22 patients with ADHD induced by levodopa-induced dyskinesia, the risk of ADRs in CC or CC CT genotype carriers was significantly reduced. After correction, OR = 0.131 / 0.106 / 0.118.rs4680GAGG or GG GA genotype carriers also significantly decreased the risk of ADRs in patients with dyskinesia. The corrected OR was 0.110 / 0.123 / 0.118.The haplotypes were found to be G-C-G-GG, A-T-C-AnMU. A-C-C-GGG) and A-T-C-G with frequencies greater than 0.01. The distribution frequencies of M / M haploid genotypes were 3.0vs13.66.After correction, the frequencies of M / M haploid genotypes were 3.0vs13.66.After correction, the frequencies of M / M haploid genotypes were 3.0vs13.61.After correction, the frequencies of M / M haploid genotypes were 3.0vs13.61.After correction, the frequencies of M / M haploid genotypes were 3.0vs13.61.After correction, the frequencies of M / M haploid genotypes of G-C-@@. Other polymorphic loci of COMT and their haplotypes were found in healthy subjects and patients with EOPD LOPD. There was no significant difference in distribution between non-and non-motile groups. Conclusion the M / M haploid genotype carriers have a tendency to reduce the risk of early onset PD in the population of 1: COMT. However, the risk of dyskinesia was significantly increased in patients with hyperactivity disorder. Rs4633CTCC or CC CT genotype rs4680GAGG or GGGA genotype carriers had significantly lower risk of dyskinesia with other polymorphic loci and their haplotypes in COMT compared with Han nationality in China. There was no significant correlation between disease susceptibility and levodopa-induced dyskinesia in patients with sporadic Parkinson's disease.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742.5

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