本文選題：帕金森病　切入點：COMT　出處：《中南大學》2014年碩士論文

【摘要】：目的：研究COMT基因rs6269, rs4633, rs4818和rs4680多態(tài)性及其構成的單倍型與帕金森病的易患性及左旋多巴誘導的異動癥的相關性。 方法：rs6269和rs4633采用PCR-RFLP方法,rs4818和rs4680采用直接測序法對188名帕金森病患者和111名健康對照者進行基因分型�；颊吒鶕欠癯霈F左旋多巴誘導的異動癥分為非異動組和異動組。 結果：在早發(fā)帕金森病組中,A-T-C-A/A-T-C-A (M/M)型患者的分布頻率比對照組低,具有邊緣統(tǒng)計學意義(P=0.050),可能減少早發(fā)帕金森病發(fā)生的風險(校正后OR=0.062)。最終入組的188例患者中,有22例出現了左旋多巴誘導的異動癥。rs4633CT、CC或者CC+CT基因型攜帶者出現異動癥不良反應的風險明顯降低,校正后OR分別為0.131、0.106、0.118。rs4680GA、GG或者GG+GA基因型攜帶者出現異動癥不良反應的風險也明顯降低,校正后OR分別為0.110、0.123、0.118。單倍型分析中發(fā)現G-C-G-G(H)、 A-T-C-A(M).A-C-C-G(L)及A-T-C-G共4個頻率大于0.01的單倍型,M/M單倍體基因型在非異動組和異動組的分布頻率分別為(3.0%vs13.6%),經校正后P=0.046,OR=9.433在異動和非異動組的分布具有統(tǒng)計學差異。COMT其他的基因多態(tài)性位點及其構成的單倍型在健康受試者和PD、EOPD、LOPD患者之間,非異動和異動組之間的分布均沒有顯著性差異。 結論：COMT中M/M單倍體基因型攜帶者有減少早發(fā)型PD發(fā)生風險的趨勢,但出現異動癥的風險則明顯增加。rs4633CT、CC或者CC+CT基因型,rs4680GA、GG或者GG+GA基因型攜帶者出現異動癥的風險明顯降低；COMT中其他基因多態(tài)性位點及其構成的單倍型則與中國漢族人群中散發(fā)性帕金森病患者的疾病易感性和左旋多巴誘導的異動癥的發(fā)生沒有明顯相關性。
[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.
【學位授予單位】：中南大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R742.5

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本文編號：1680231