本文選題：帕金森病　切入點(diǎn)：COMT　出處：《中南大學(xué)》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(gòu)成的單倍型與帕金森病的易患性及左旋多巴誘導(dǎo)的異動(dòng)癥的相關(guān)性。 方法：rs6269和rs4633采用PCR-RFLP方法,rs4818和rs4680采用直接測(cè)序法對(duì)188名帕金森病患者和111名健康對(duì)照者進(jìn)行基因分型。患者根據(jù)是否出現(xiàn)左旋多巴誘導(dǎo)的異動(dòng)癥分為非異動(dòng)組和異動(dòng)組。 結(jié)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(duì)照組低,具有邊緣統(tǒng)計(jì)學(xué)意義(P=0.050),可能減少早發(fā)帕金森病發(fā)生的風(fēng)險(xiǎn)(校正后OR=0.062)。最終入組的188例患者中,有22例出現(xiàn)了左旋多巴誘導(dǎo)的異動(dòng)癥。rs4633CT、CC或者CC+CT基因型攜帶者出現(xiàn)異動(dòng)癥不良反應(yīng)的風(fēng)險(xiǎn)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(xiàn)異動(dòng)癥不良反應(yīng)的風(fēng)險(xiǎn)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(xiàn)G-C-G-G(H)、 A-T-C-A(M).A-C-C-G(L)及A-T-C-G共4個(gè)頻率大于0.01的單倍型,M/M單倍體基因型在非異動(dòng)組和異動(dòng)組的分布頻率分別為(3.0%vs13.6%),經(jīng)校正后P=0.046,OR=9.433在異動(dòng)和非異動(dòng)組的分布具有統(tǒng)計(jì)學(xué)差異。COMT其他的基因多態(tài)性位點(diǎn)及其構(gòu)成的單倍型在健康受試者和PD、EOPD、LOPD患者之間,非異動(dòng)和異動(dòng)組之間的分布均沒有顯著性差異。 結(jié)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(fēng)險(xiǎn)的趨勢(shì),但出現(xiàn)異動(dòng)癥的風(fēng)險(xiǎn)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(xiàn)異動(dòng)癥的風(fēng)險(xiǎn)明顯降低；COMT中其他基因多態(tài)性位點(diǎn)及其構(gòu)成的單倍型則與中國(guó)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(dǎo)的異動(dòng)癥的發(fā)生沒有明顯相關(guān)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(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R742.5

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 ;SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci[J];Cell Research;2005年02期

2 劉英姿;劉潔;周宏灝;;帕金森病藥物治療的遺傳藥理學(xué)研究進(jìn)展[J];中國(guó)藥理學(xué)通報(bào);2009年10期

3 金遠(yuǎn)香;劉潔;;COMT的遺傳藥理學(xué)研究進(jìn)展[J];中國(guó)藥理學(xué)通報(bào);2013年08期

，

本文編號(hào)：1680231