5，10亚甲基四氢叶酸还原酶基因C677T多态性与帕金森病伴发高同型半胱氨酸血症的关系  

Association between methylenetetrahydrofolate reductase gene C677T polymorphism and Parkinson＇ s disease combined with hyperhomocysteinemia

作　　者：晁宁[1] 孙亮 于会艳[1] 赵丽姣[1] 曾湘豫[1] 顾卫红[3] 杨泽 秦斌[1] 

机构地区：[1]卫生部北京医院神经内科,100730 [2]老年医学研究所遗传室 [3]北京中日友好医院神经内科

出　　处：《中华老年医学杂志》2014年第2期121-125,共5页Chinese Journal of Geriatrics

摘　　要：目的研究5，10亚甲基四氢叶酸还原酶（MTHFR）基因C677T多态性与帕金森病（PD）患者伴发高同型半胱氨酸血症（HHcy）的关系。方法收集2011年5月至2013年3月在我院神经内科住院及门诊的PD患者161例作为PD组，同期在我院体检中心健康体检者240例作为对照组，对两组C677T多态性进行基因分型，测定患者同型半胱氨酸（Hcy）、叶酸、维生素B12水平，比较C677T多态性基因型与等位基因在PD组和对照组问分布规律；同时通过进行不同Hcy水平患者不同遗传模型分析和Logistic回归模型校正，综合研究C677T多态性与PD患者伴发HHcy的关系。结果PD组与对照组C677T位点的基因型及等位基因的分布差异均无统计学意义（X2=0．21、0．14，P=0．901、0．710）；对PD组按Hcy水平进行分层分析结果显示，基因型及等位基因在HHcy组和Hcy正常组的频率分布差异有统计学意义（X2=11．32、6．74，P=0．003、0．009）。比较HHcy组和Hcy正常组C677T多态性的分布结果显示，隐性模型下TT型和CT＋CC型频率分布差异有统计学意义（X2=11．15，P=0．001）；在纯合子模型下，CC型与TT型分布差异有统计学意义（X2=6．02，P=0．014）。Logistic回归分析校正年龄、性别、叶酸、维生素B12、左旋多巴治疗情况等混杂因素后，C677T多态性的T等位基因隐性模型、纯合子模型是PD患者发生HHcy的危险因素（OR=6．83、6．86，P=0．001、0．006）。结论MTHFR基因C677T多态性与PD发病可能不相关，但C677T多态性的T等位基因可能是PD伴发HHcy的独立危险因素。Objective To study the association between the methylenetetrahydrofolate reductase （MTHFR） gene C677T polymorphism and Parkinson＇ s disease （ PD ） combined with hyperhomocysteinemia（HHcy）. Methods Based on high-resolution melting（HRM） curve analysis, 240 health controls（control group） and 161 patients with Parkinsonrs disease（case group） were genotyped for C677T polymorphism. The levels of plasma homocysteine（Hcy）, folateand vitamin B12 were determined. The C677T polymorphism distribution was compared between case and control groups. The patients in case group were stratified by homocysteine level： ≥15/μmol/L was considered as hyperhomocysteinemia（HHcy group）, and〈15μmol/L was considered as normal homocysteine level（normal Hcy group）. The frequency distribution of C677T genotypes and alleles were compared between the two subgroups. By means of different genetic model and logistic regression analysis, a comprehensive analysis of association was conducted between C677T genotypes and PD patients with HHcy. Results There were no significant differences in MTHFR gene C677T alleles and genotypes between case and control groups（X2=0.21 and 0. 14, both P^O. 05）. When stratified by Hcy level, the frequency distributions of C677T alleles and genotypes were significantly different between HHcy group and normal Hey group（X2= 11.32 and 6.74, both P^0.01）. There were significant differencesin the frequency distributions of TT and CT q-CC genotypes in recessive model and CC and TT genotypes in homozygous model between HHcy group and normal Hcy group（X2= = 11.15 and 6.02, P d0.01 or 0.05）. After adjusting for confounding factors including age, sex, L-Dopa treatment, folate and vitamin Blz levels, logistic regression analysis showed that the C677T polymorphism of T alleles in recessive and homozygous models was the risk factor for HHcy in PD patients（OR= 6.83 and 6.86, both P^0.01）. Conclusions There is no association between MTHFR gene C677T polymorphism and PD. Howev

关 键 词：帕金森病 高同种半胱氨酸血症 多态性 单核苷酸 

分 类 号：R742.5[医药卫生—神经病学与精神病学]