MTHFR基因多态性及血浆同型半胱氨酸水平与冠心病的关系

目的研究亚甲基四氢叶酸还原酶（m ethylenetetrahydrofolate reductase,MTHFR）基因677位单核苷酸多态性（C-T）与血浆同型半胱氨酸（homocyste ine,Hcy）水平及冠心病之间的关系。方法用多聚酶链式反应-限制性片段多态性（RFLP）方法检测122例冠心病患者（冠脉造影显示至少有1支血管狭窄≥50%）与56例对照组（冠脉造影未发现任何可辨认斑块或狭窄）的MTHFR 677位单核苷酸多态性（C-T）;用荧光衍生化后高效液相色谱法（h igh?perform ance liqu id chrom atography,HLPC）检测血浆总Hcy水平。结果①冠心病组Hcy浓度高于对照组（P<0.05）。②冠心病组中TT、TC、CC的基因型频率分别为30%、45%、25%;T等位基因频率为53%,C等位基因频率为47%。在对照组中TT、TC、CC的基因型频率分别为25%、32%、43%;T等位基因频率为41%,C等位基因频率为59%。两组基因型分布和等位基因频率分布差异有显著性（均P<0.05）。③两组的TT基因型者血浆Hcy浓度均显著高于CC和TC基因型者（P<0.05）,而后两者间无显著性差异。结论MTHFR基因C677T点突变对冠心病发病有一定的关系。MTHFR基因纯合突变是引起高Hcy血症的一个重要的遗传因素。     

N5，N10-亚甲基四氢叶酸还原酶基因多态性及血浆同型半胱氨酸与冠心病的关系

目的研究N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性、血浆同型半胱氨酸(Hcy)与冠心病的关系。方法选取2013年至2015年在我院住院的冠心病患者256例,按年龄分为60岁组(中青年组)107例及≥60岁组(老年组)149例,选取同期行健康体检的人群145例作为对照组,应用聚合酶链反应(PCR)技术和基因芯片分析技术检测MTHFR基因C677T多态性,应用高效液相色谱法测定血浆Hcy水平,分析不同组群之间MTHFR基因C677T多态性的分布及Hcy水平。结果 MTHFR基因分布频率:中青年组CC型、CT型、TT型基因频率分别为26.2%,43.9%,29.9%,C等位基因频率为48.1%,T等位基因频率为51.9%。中青年组CC型、CT型、TT型基因频率分别为35.6%,42.3%,22.1%,C等位基因频率为56.8%,T等位基因频率为43.2%。对照组CC型、CT型、TT型基因频率分别为37.9%,40.1%,21.4%,C等位基因频率为58.3%,T等位基因频率为41.7%。中青年组T等位基因频率明显高于对照组(χ~2=5.10,P=0.015),中青年组Hcy浓度明显高于对照组。老年组T等位基因频率与对照组比较差异无显著性(χ~2=0.147,P=0.382),两组间Hcy浓度差异无显著性。各组的TT基因型者血浆Hcy浓度均明显高于CC和TC基因型者(P0.01),而后两者间差异无显著性。结论 MTHFR基因TT型可导致Hcy水平明显升高,MTHFR基因C677T点突变仅与中青年组冠心病患者相关,与老年组冠心病患者无明显相关,Hcy水平升高及MTHFR基因T等位基因频率增高可能为中青年冠心病患者的危险因素,提示不同年龄阶段的冠心病患者发病的机制可能存在差异。     

不同类型脑梗死Hcy水平及MTHFR基因多态性

目的探讨血浆同型半胱氨酸（Hcy）水平、亚甲基四氢叶酸还原酶（MTHFR）基因多态性与不同类型脑梗死的关系。方法采用荧光偏振免疫法及PCR-限制性内切酶片段长度多态性技术分别检测脑血栓形成、腔隙性脑梗死患者及健康对照者的血浆Hcy水平及MTHFR C677T基因多态性。结果脑血栓形成患者的TT基因型及T等位基因频率均显著高于对照组（P〈0.05）,脑血栓形成及腔隙性脑梗死患者血浆Hcy水平均显著高于对照组（P〈0.05）。结论血浆Hcy水平升高是脑血栓形成及腔隙性脑梗死的危险因素。MTHFR基因677TT型可引起血浆Hcy水平升高,是脑血栓形成的危险因素。     

血浆同型半胱氨酸及5,10-亚甲基四氢叶酸还原酶基因多态性与老年原发性高血压合并冠心病的关系

目的探讨血浆同型半胱氨酸(Hcy)水平及其代谢酶5,10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性与老年原发性高血压合并冠心病的关系。方法选择2014年2月~2015年2月于玉林市第一人民医院心内科住院的老年原发性高血压患者共200例,其中男性115例,女性85例,平均年龄(67.52±3.53)岁。根据冠状动脉造影结果分为高血压组(100例)及冠状动脉粥样硬化性心脏病(冠心病)组(100例)。选取同时期的健康体检者100例为对照组。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法检测3组MTHFR C677T基因型,同时检测Hcy水平。结果与对照组比较,高血压组和冠心病组血压、三酰甘油、总胆固醇、低密度脂蛋白胆固醇、Hcy均升高,差异有统计学意义(P均0.05)。高血压组MTHFR C677位点CC、CT和TT基因型频率分别为27.0%、50.0%和23.0%,C和T等位基因频率分别为52.0%和48.0%。冠心病组CC、CT和TT基因型频率分别为12.0%、55.0%和33.0%,C和T等位基因频率分别为39.5%和60.5%。对照组CC、CT和TT基因型频率分别为40.0%、45.0%和15.0%,C和T等位基因频率分别为62.5%和37.5%。冠心病组TT型基因频率及T等位基因频率均高于高血压组和对照组,差异有统计学意义(P均0.05)。冠心病组患者TT型Hcy水平高于CC型和CT型,差异有统计学意义(P均0.05)。结论 MTHFR C677T基因多态性中TT基因型可能是老年原发性高血压合并冠心病的一个重要遗传风险因子,T等位基因可能为该病的风险等位基因。     

MTHFR基因多态性及血浆同型半胱氨酸与老年脑梗死的相关性研究

目的探讨N5，N10亚甲基四氢叶酸还原酶（MTHFR）基因多态性及血浆同型半胱氨酸（Hcy）与老年脑梗死的相关性。方法应用高效液相色谱法和多聚酶链反应限制性内切酶片段长度多态性技术检测并比较了102例老年脑梗死患者（脑梗死组）和100例健康老年人（对照组）的血浆Hcy浓度及MTHFR基因型。结果两组MTHFR677位点基因型分布和各等位基因频率比较均有统计学差异（P均〈0．05）；脑梗死组T等位基因频率及血浆Hcy浓度高于对照组（P均〈0．05）。结论MTHFR基因突变可导致血浆Hcy浓度升高，高Hcy浓度及MTHFR基因T型均为老年脑梗死的高危因素。     

MTHFR基因多态性与急性心肌梗死的相关性分析

目的：研究同型半胱氨酸浓度及MTHFR基因多态性与急性心肌梗死（Acute myocardial infarction, AMI）之间的相关性。方法 ：选取我院2013年10月~2016年4月在我院就诊的60例AMI患者作为实验组,其中男性37例,女性23例,平均年龄66.3±10.4岁。选取同期我院行健康体检的人群60例作为对照组,其中男性39例,女性21例,平均年龄68.7±11.1岁。分别测定两组血浆同型半胱氨酸（Homocysteine,Hcy）浓度、叶酸浓度水平以及MTHFR基因的多态性。分析两组之间MTHFR基因 C677T 多态性的分布及 Hcy 水平。 结果：AMI组血浆Hcy浓度水平(18.74±3.71umol/L)明显高于对照组(10.74±5.11umol/L),差异具有明显统计学意义（P＜0.05）;AMI组患者的叶酸浓度水平(4.87±3.16ng/ml)明显低于对照组(9.71±2.97ng/ml)（P＜0.05）;叶酸与Hcy浓度水平之间呈负相关性;AMI组患者的MTHFR基因TT纯合子组的血浆Hcy水平(19.74±3.16umol/L)与CT杂合子(13.68±3.94umol/L)和CC纯合子(12.41±1.54umol/L)相比明显增高（P＜0.05）;与健康对照组相比AMI组TT纯合子的分布频率(AMI组36.67%,对照组16.67%)明显增高（P＜0.05）;并且AMI组的T等位基因频率（AMI组58.33%,对照组38.33%）明显增高（P＜0.05）。结论：Hcy在血浆中的浓度水平与AMI的发病之间有着密切的联系,MTHFR基因的多态性与AMI易感性密切相关,MTHFR基因T等位基因可能是导致AMI的风险基因突变。     

同型半胱氨酸及其代谢酶基因多态性与冠心病的关系

目的探讨血浆同型半胱氨酸(Hcy)水平及其代谢酶MTHFR C677T、MTHFR A1298C、MS A2756G、MTRR A66G基因多态性与冠心病的相关性。方法在川东北地区汉族人群中221例冠心病患者(冠心病组)和与之性别、年龄匹配的210例非冠心病患者(对照组)为研究对象。采用Hcy检测试剂盒(速率法)测定两组患者血浆Hcy水平,采用改良多重连接反应检测技术(i MLDR)检测目的基因,进行单核苷酸多态性(SNP)分型,分析两组之间Hcy水平及其Hcy代谢酶基因多态性分布情况。结果 (1)冠心病组血浆Hcy水平明显高于对照组(15.39±6.89μmol/L比12.90±6.44μmol/L,P0.05),Hcy在两组之间比较OR值为1.060(95%CI 1.021~1.100),差异具有统计学意义(P0.05)。(2)MTHFR C677T、MTHFR A1298C、MS A2756G、MTRR A66G在两组之间比较,无论是基因型分布频率还是等位基因分布频率均无统计学差异(P均0.05);基因-基因间交互作用分析发现,这四个基因位点在冠心病的发病过程中不存在交互作用(P0.05);基因-环境间交互作用分析发现,MTHFR C677T与吸烟、甘油三酯之间也不存在交互作用(P均0.05)。(3)血浆Hcy水平在冠心病MTHFR TT基因型组(19.72±11.51μmol/L)最高,且分别高于CC基因型组(13.99±4.77μmol/L,P0.05)及CT基因型组(15.44±6.25μmol/L,P0.05)。结论 Hcy可能增加川东北地区汉族人群冠心病的患病风险,MTHFR C677T TT基因型的冠心病患者血浆Hcy水平较高,未发现MTHFR C677T、MTHFR A1298C、MS A2756G、MTRR A66G基因多态性与冠心病发病相关。     

亚甲基四氢叶酸还原酶基因多态性与原发性高血压患者合并冠心病的相关性研究

目的探讨N5,10-亚甲基四氢叶酸还原酶(MTHFR)C677T位点突变与河南豫北地区原发性高血压及其合并冠心病发病的关系。方法选择原发性高血压患者405例为高血压组,高血压合并冠心病患者400例为冠心病组,健康体检者400例为对照组。对3组MTHFR基因C677T多态性进行基因分型。结果冠心病组T等位基因频率和TT基因型频率明显高于高血压组和对照组(P<0.05)。冠心病组TT基因型患者TC和血浆同型半胱氨酸水平明显高于CC+CT基因型(P<0.05)。结论 MTHFR基因C677T多态性与原发性高血压患者冠心病的发生相关。     

急性脑梗死患者MTHFR基因多态性与血浆同型半胱氨酸水平的关系

目的 探讨急性脑梗死（ACI）患者N5,N10-亚甲四氢叶酸还原酶（MTHFR）基因多态性与血浆同型半胱氨酸（Hcy）水平的关系.方法 采用多聚酶链反应2-限制性内切酶片段长度多态性技术（PCR2-RFLP）检测48例ACI患者MTHFR基因C677T位点多态性,同时测定血浆总Hcy及血清叶酸、维生素B12、尿酸（UA）.结果 ACI患者MTHFR基因T/T型频率为35.43％,T/C型频率为56.32％,C/C型频率为8.25％;T等位基因频率为63.59％,C等位基因频率为36.41％.MTHFR基因T/T型ACI患者血浆Hcy显著高于其他两型,T/C型与C/C型血浆Hcy水平较比较无显著差异.Hcy中度与轻度增高者MTHFR基因分布比较,P≤0.05.3组基因型间叶酸、维生素B12及UA水平均无显著差异.结论 ACI患者MTHFR基因C677T突变与Hcy水平显著相关,MTHFR基因纯合突变可能是引起高Hcy的一个重要遗传因素.     

同型半胱氨酸代谢异常与冠心病的关系

目的：探讨同型半胱氨酸代谢异常与冠心病的关系。方法：选择245例健康对照者和入住我院冠心病房的439例经冠状动脉造影证实为冠心病者作为研究对象，监测其血浆同型半胱氨酸（Hcy）、叶酸和VitB12水平，分析亚甲基四氢叶酸还原酶（MTHFR）基因多态性，并根据冠状动脉造影结果，分成单支、双支和三支病变组，分析病变支数与MTHFR基因多态性的关系。结果：冠心病患者血浆Hcy水平（17．61＋11．62）显著高于对照组（12．92＋8．23）（P〈0．001），叶酸和VitBl2水平低于对照组（P〈0．05）。冠心病组TT基因型明显高于对照组（P〈0．05），冠心病组中三支血管病变组的TT基因频率比单支和双支血管病变组高（P〈0．005），TT型纯合子的血浆Hcy含量与CC型纯合子和CT杂合子比较具统计学差异（P〈0．001），而叶酸和VitB12含量低于后两者（P〈0．05）。结论：血浆Hcy含量和MTHFR基因突变相关，其TT纯合子血浆Hcy水平最高，而在三支血管病变组的TT基因频率最高，提示MTHFR基因突变可导致Hcy水平升高，是冠心病的危险因素。     

冠心病患者亚甲基四氢叶酸还原酶基因多态性87例研究

目的探讨N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性与冠心病的关系。方法对2003年11月至2005年8月贵阳医学院附属医院及贵州市第二人民医院住院的87例冠心病患者(冠心病组)及同期在门诊进行健康体检的73名健康人(对照组),采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测其MTHFRC677T基因多态性。结果对照组与冠心病组MTHFR677位T等位基因的分布频率分别是18.5%,36.1%,病例组MTHFR基因C677T的CT基因型及T等位基因频率显著高于对照组,差异有显著性(P<0.05)。结论MTHFRC677T基因多态性与冠心病密切相关。     

Methylenetetrahydrofolate reductase polymorphism associated with susceptibility to coronary heart disease in Chinese type 2 diabetic patients

OBJECTIVE: Epidemiological studies have identified hyperhomocyst(e)inemia as an independent risk factor for atherosclerosis. The C677T variant of the methylenetetrahydrofolate reductase (MTHFR) gene, one of the key enzymes catalyzing remethylation of homocysteine, might play a role in the development of coronary heart disease (CHD). In this study, we examined the distribution of the MTHFR genotypes in the Chinese population and the association between the C677T variant and CHD in Chinese type 2 diabetic patients. METHODS: Two hundred and twenty-eight unrelated patients with type 2 diabetes mellitus (126 with coronary heart disease) and 114 healthy control subjects were recruited. The MTHFR genotype was analyzed by PCR followed by HinfI digestion. Plasma total homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. RESULTS: In 114 healthy control subjects, the frequency of the mutant T allele was 38.0%, comparable to that of a Hong Kong (Chinese) population. The genotype distribution did not differ between control subjects and type 2 diabetic patients (chi(2) = 3.67, P > 0.05). Genotypic analysis revealed that type 2 diabetic patients with CHD displayed a greater prevalence of T allele (45.2%) than type 2 diabetic patients without CHD (30.4%) (chi(2) = 8.72, P < 0.005). The odds ratio for CHD in type 2 diabetic patients in presence of T allele was 1.89 (CI 95%, 1.24-2.88). The MTHFR genotype were different between diabetic patients with and without CHD (chi(2) = 11.98, P < 0.005). Moreover, plasma homocysteine levels were markedly higher in individuals with TT genotype than those with CC or CT genotype or CC plus CT genotype. CONCLUSIONS: The C677T mutation of MTHFR gene is common in the Chinese population. MTHFR C677T gene polymorphism associated with a predisposition to increased plasma homocysteine levels could constitute a useful predictive marker for CHD in Chinese type 2 diabetic patients.     

C677T gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) in patients with myocardial infarction

Hyperhomocysteinemia is thought to be an independent risk factor for coronary heart disease. Increased plasma homocysteine level can result from malnutrition (e.g. folate deficiency) and/or genetic-related disturbances. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the synthesis of 5-methyltetrahydrofolate, the methyl donor for homocysteine remethylation to methionine. Transition of cytosine (C) to thymidine (T) at nucleotide position 677 of MTHFR gene causes alanine 226-to-valine substitution, and in consequence results in decreased enzyme activity and increased homocysteine level. Therefore, the aim of our study was to estimate the frequency distribution of C677T MTHFR polymorphism in patients with past myocardial infarction (MI), and to evaluate the association between this polymorphism and age of MI onset or left ventricular mass (LVM). The study was performed in 100 MI patients aged from 34 to 76 years and in control group consisted of 100 age- and gender-matched non-MI subjects. Applying PCR followed by Hinf I digestion of amplification products no significant difference in the frequency distribution of C677T MTHFR genotypes has been found between both groups (MI patients: 46% CC, 45% CT and 9% TT, and control group: 39% CC, 50% CT and 11% TT, respectively). No significant association between MTHFR genotypes and age of MI onset or LVM has been found in MI group. The results of our study suggest that C677T polymorphism of MTHFR gene is not a risk factor for myocardial infarction in Polish population.     

Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene

BACKGROUND: There is an association between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and methotrexate related toxicity. OBJECTIVE: To examine the relations between the recently described A1298C polymorphism of the MTHFR gene, plasma homocysteine, methotrexate toxicity, and disease activity in patients with rheumatoid arthritis. DESIGN: A cross sectional study on 93 methotrexate treated patients with rheumatoid arthritis, comprising a clinical interview and physical examination to determine disease activity and methotrexate related adverse reactions. Genotype analysis of the MTHFR gene was carried out and fasting plasma homocysteine and serum folate concentrations were measured. The data were analysed using univariate analysis. Allele and genotype distributions were compared with those of a healthy control group. RESULTS: The frequency of the 1298CC genotype (24.7%) in the rheumatoid study group was greater than expected in the general population (12.8%, p<0.001). This genotype was associated with a significantly low rate of methotrexate related side effects. The odds ratio for side effects in patients with wild type 1298AA genotype v 1298CC genotype was 5.24 (95% confidence interval, 1.38 to 20). No correlation of disease activity variables or plasma homocysteine with MTHFR A1298C and C677T polymorphisms was observed. CONCLUSIONS: 1298CC polymorphism was more common in methotrexate treated rheumatoid patients than expected in the population, and was associated with a reduction in methotrexate related adverse effects. The A1298C polymorphism of the MTHFR gene may indicate a need to adjust the dose of methotrexate given to patients with rheumatoid arthritis.     

亚甲基四氢叶酸还原酶基因C677T多态性与原发性高血压患者动脉顺应性的关系

目的研究亚甲基四氢叶酸还原酶基因C677T多态性与原发性高血压及动脉顺应性的关系。方法对695例原发性高血压患者和509例年龄匹配的正常对照者采用聚合酶链反应和限制片长多态性分析方法进行基因多态性分析,电泳判断基因型及测序,并测定颈动脉—桡动脉脉搏波速度和颈动脉—股动脉脉搏波速度。结果高血压组TT基因型频率和T等位基因频率显著高于正常对照组(26.5%比20.6%及48.7%比42.4%,P=0.015和0.002)。T等位基因携带者的颈动脉—股动脉脉搏波速度显著高于CC基因型者(P<0.05),高血压组颈动脉—桡动脉脉搏波速度在T等位基因携带者也显著高于CC基因型者(P=0.001)。携带T等位基因的高血压患者颈动脉—股动脉脉搏波速度及非单纯收缩期高血压患者颈动脉—桡动脉脉搏波速度均显著高于CC基因型者(P<0.05)。结论亚甲基四氢叶酸还原酶基因C677T多态性可能与原发性高血压发病危险性增加有关,并且677T等位基因可能是高血压动脉硬化的遗传因素。     

内皮型一氧化氮合酶和N5，N10-亚甲基四氢叶酸还原酶基因多态性与苏皖地区汉族人群早发冠心病易感性的相关关系

目的 探讨内皮型一氧化氮合酶(eNOS)基因第7外显子G894T突变和N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T突变与苏皖地区汉族人群早发冠心病(PCAD)发病的关系.方法 采用病例对照研究的方法,应用聚合酶链反应-限制性片长多态性(PCR-RFLP)技术,分别检测131例PCAD患者(PCAD组)和131例年龄、性别相匹配的无冠心病者(对照组)的eNOS和MTHFR基因的单核苷酸多态性,判定其基因型并统计各基因型及等位基因的频率.结果 eNOS基因G894T多态性在PCAD组和对照组中的基因型分布(x2=2.072,P=0.355)和T等位基因频率(x2=0.727,P=0.394)差异均无统计学意义.MTHFR基因C677T基因型在PCAD组CT和TT型分布均高于对照组(x2 =14.290,P=0.001),T等位基因频率亦高于对照组(x2=16.339,P =0.000),差异有显著性(P＜0.05).Logistic回归分析显示,携带MTHFR基因C677TTT基因型是PCAD发病的独立危险因素.结论 eNOS基因G894T多态性可能与苏皖地区汉族人群PCAD发病无关;MTHFR基因677C/T多态性的TT基因型可能增加苏皖地区汉族人群PCAD的患病风险,T等位基因可能是PCAD的遗传易感基因.     

Methylenetetrahydrofolate reductase gene polymorphism and risk of premature myocardial infarction

BACKGROUND: Elevated plasma homocysteine level is an independent risk factor for cardiovascular disease. A common mutation (nucleotid 677C-T) in the gene coding for methylenetetrahydrofolate reductase (MTHFR) has been reported to reduce the enzymatic activity of MTHFR and is associated with elevated plasma levels of homocysteine, especially in subjects with low folate intake. HYPOTHESIS: Methylenetetrahydrofolate reductase T/T genotype may be a risk factor for premature MI in Turkish population who are known to have low folate levels. METHODS: The study group was comprised of 96 men (aged <45 years) with premature myocardial infarction (MI) and 100 age- and gender-matched controls who had no history or clinical evidence of coronary artery disease (CAD) and/or MI. DNA was extracted from peripheral blood and genotypes were determined by polymerase chain reaction, restriction mapping with HinfI, and gel electrophoresis. Conventional risk factors for CAD were prospectively documented. RESULTS: Allele and genotype frequencies among cases and control subjects were compatible with Hardy-Weinberg equilibrium. The frequencies of T/T, C/T, and C/C genotypes among patients with MI and control subjects were 15.6, 40.6, and 43.8%, and 5, 35, and 60%, respectively. Multivariate analyses identified smoking, MTHFR C/T polymorphism, diabetes mellitus, family history of CAD, and hypertension as the independent predictors of premature MI. Defining patients with non-T/T genotype (C/C and C/T combined) as reference, the relative risk of MI for subjects with T/T genotype was 5.94 (95% confidence interval: 1.96-18.02, p = 0.0016). CONCLUSIONS: Our findings suggest that C677T transition in the MTHFR gene may be a risk factor for premature MI in Turkish men.     

Does the polymorphism 677C-T of the 5,10-methylenetetrahydrofolate reductase gene contribute to homocysteine-related vascular disease?

Whether the 677C-T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene acts as a risk factor for homocysteine-related vascular disease remains a matter of debate. Testing for the 677C-T nucleotide substitution and assay of plasma homocysteine were carried out simultaneously in 69 controls and 113 vascular disease patients from the Paris area. The variant gene frequency as well as the variant homozygous genotype frequency were very similar in controls and patients. Conversely, plasma homocysteine levels were substantially higher in patients than in controls. A slight interaction between the 677C-T MTHFR polymorphism and homocysteinaemia was observed in the patient group only, while a negative correlation between fasting homocysteine and plasma folate levels was found in all individuals homozygous for the 677C-T MTHFR genotype, irrespective of vascular disease. These data suggest that the 677C-T MTHFR polymorphism is not a major determinant of the vascular disease but contributes to increased plasma homocysteine concentration in conjunction with low plasma folate levels.     

类风湿关节炎合并心血管病变患者血清同型半胱氨酸水平及其与亚甲基四氢叶酸还原酶基因多态性的关系

目的检测类风湿关节炎（RA）患者血清同型半胱氨酸水平和亚甲基四氢叶酸还原酶（MTHFR）基因单核苷酸多态性,分析其在RA合并心血管病变患者中的作用。方法收集183例RA患者,分为合并心血管病变组和无心血管病变组,同时选取50名我院健康体检者作为对照组。采用实时荧光定量聚合酶链反应方法测定RA患者和对照组的MTHFR基因rs1801133C／T（677）和rs1801131A／C（1298）2个位点的基因单核苷酸多态性;ELISA法检测3组受试者血清同型半胱氨酸水平。结果①183例RA患者心血管病变发生率约为29．0％,其中合并心血管病变组同型半胱氨酸水平明显高于无心血管病变组（P〈0．001）。②677TT基因型组血清同型半胱氨酸水平高于CC及CT组（P〈0．05）。③RA患者血清同型半胱氨酸水平与心血管事件呈正相关。结论RA合并心血管病变患者血清同型半胱氨酸水平明显高于RA无心血病变组及正常对照组,其水平增高可能与MTHFR677C／T基因多态性有关。血清同型半胱氨酸水平升高可作为RA患者发生心血管事件的预测指标。