ALOX5AP基因多态2354T/A和MTHFR基因多态677C/T的协同作用显著增加脑梗塞的易患性

目的研究MTHFR多态性和编码5-脂氧合酶激活蛋白的基因ALOX5AP多态性，尤其是基因之间的相互作用，是否与脑卒中的易患性相关。方法采用PCR．RFLP方法，对来自7个临床中心的1823名对照和1832名脑卒中患者检测了基因ALOX5AP和MTHFR的3个多态性，基因分型结果经测序进一步确证。多元logistic回归方法校正了传统危险因素后分析基因多态性与脑卒中的独立相关性。检测7个与脑卒中不相关的微卫星多态标记在病例一对照人群的频率分布以评估人群层化程度。结果MTHFR677TT基因型与男性脑梗塞的发病风险呈弱相关（OR，1．45；95％CI：1．04-2．02；P=0．020），ALOX5AP2354AA基因型也增加男性脑梗塞1．55倍的发病风险（95％CI：1．03．2．35；PP=0．038）。当个体同时携带MTHFR677TT和ALOX5AP2354AA基因型时，男性脑梗塞的相对患病风险率显著增加至3．58倍（（95％CI：1．72-7．43；P=0．001）。微卫星多态性标记的各主要等位基因片段的频率在病例和对照组无显著性差异。结论MTHFR677TT基因型和ALOX5AP2354AA基因型的协同作用与增加的男性脑梗塞患病风险呈显著相关。对于多因素复杂性疾病，综合分析弱效基因的相互作用有助于了解个体易患脑卒中的遗传背景。     

叶酸代谢基因及血浆同型半胱氨酸在老年脑卒中患者中的表达及相关性

目的 探讨四氢叶酸还原酶(MTHFR)C677T位点、甲硫氨酸合成酶还原酶(MTRR A66G位点及血浆同型半胱氨酸(Hcy)在老年脑卒中患者中的表达及相关性。方法 选取2018年1月到2019年6月西宁市第二人民医院收治的80例老年脑卒中患者作为脑卒中组,另选择我院同期体检的73例健康人员作为对照组。采用PCR-RELP法检测患者MTHFR C677T位点和MTRR A66G位点基因多态性,采用全自动生化仪检测血浆Hcy水平,分析不同MTHER、MTRR基因型、血浆Hcy水平与脑卒中关系。结果 脑卒中组TT型、GG型基因频率均高于对照组,CC型、AA型基因频率低于对照组(t=12.771、4.408、4.912、3.921,P 0.05)。脑卒中组各基因型Hcy水平均高于对照组,差异具有统计学意义(t=6.477、10.663、4.227、2.685、2.949、3.929,P 0.05),两组MTHFR C677T的TT型患者Hcy水平均高于CT型、CC型,差异具有统计学意义(P 0.05);两组MTRR A66G位点GG型患者Hcy水平均高于AG型、AA型,差异具有统计学意义(P 0.05)。Spearman相关性分析显示,MTHFR C677T位点、MTRR A66G位点各基因型频率均与Hcy水平呈正相关(r=0.779、0.684、0.716、0.806、0.758、0.818,P 0.05);Logistic回归分析显示,MTHFR C677T位点TT型、Hcy水平是影响脑卒中发生的危险因素[OR (95%CI)=3.167(1.421～5.385)、2.822(1.652～4.770),P 0.05]。结论 老年脑卒中患者MTHFR C677T位点TT型、MTRR的A66G位点GG型基因频率、血浆Hcy水平高于健康人群,其中MTHFR C677T位点TT型基因频率、血浆Hcy水平是影响脑卒中发生的重要因素。     

汉族脑卒中与N5,N10亚甲基四氢叶酸还原酶基因多态性的相关性研究

目的　探讨人体 N5,N1 0亚甲基四氢叶酸还原酶 (MTHFR)的基因多态性与脑卒中的遗传相关性。方法　采用限制性内切酶片段长度多态性方法 (PCR- RFLP) ,对 67例脑卒中病人和 78例健康人 MTHFR基因 C677T多态性位点进行检测。结果　病例组 MTHFR基因 T、C等位基因频率分别为 53%、47%,对照组为 39.7%、60 .3%,两组显著性差异 (χ2 =5.0 9,P<0 .0 5)。 TT型携带者较 CC型携带者罹患脑卒中的相对风险度为 2 .35(95%CI1 .0 2～ 5.43)。 T等位基因携带者较 C等位基因携带者罹患脑卒中的相对风险度为 1 .71 (95%CI1 .0 7～ 2 .74)。出血性卒中与缺血性卒中之间等位基因及等位基因型频率无明显差异。结论　脑卒中汉族人群 MTHFR基因 C677T位点多态性与脑卒中有相关性 ,MTHFR基因可能是脑卒中的一个易感基因。     

MTHFR基因多肽性及血浆同型半胱氨酸水平与老年人脑卒中发病的关系

目的：探讨N^5，N^10-亚甲基四氢叶酸还原酶（MTHFR）基因C677T位点突变和血浆总同型半胱氨酸（tHcy）水平升高是否增加中国老年人群脑卒中的危险。方法：对1002例经头颅CT确诊的老年（〉60岁）脑卒中患者和948例非卒中对照者，采用多聚酶链反应．限制性内切酶片段长度多态性技术（PCR-RFLP）检测MTHFR C667T基因型，用高效液相色谱法测定血浆总同型半胱氨酸水平，同时所有研究对象记录其病史，体检等临床资料及吸烟，饮酒等流行病学资料。结果：脑卒中患者MTHFR基因纯合子突变（TT）和杂合子突变（CT）发生率（69．4％）明显高于对照组（64．3％，P=0．016），卒中组T等位基因频率（45．8％）也高于对照组（42．4％，P=0．032）；脑卒中患者血浆总同型半胱氨酸水平及异常检出率和中、重度增高率亦明显高于对照组（P〈0．001），且MTHFR基因TT型〉CT型〉CC型（P〈0．001）。Logistic回归分析结果显示：在调整传统危险因素后，升高的tHey水平和CT和TT基因型仍与脑卒中发病的有关，且血浆同型半胱氨酸水平越高发生脑卒中的危险性越大。结论：高同型半胱氨酸血症是中国老年人脑卒中发病的一个独立危险因素，而MTHFR基因C677T位点突变可能是其发病的重要遗传因素。     

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对脑卒中合并H型高血压病人治疗效果的影响

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T位点多样性对脑卒中合并H型高血压病人治疗效果的影响。方法:纳入2020年9月—12月承德医学院附属医院收治的120例脑卒中合并H型高血压病人,所有病人均给予高血压常规治疗及脑卒中二级预防治疗,在此基础上给予叶酸、维生素B₆和甲钴胺片联合治疗。比较不同MTHFR C677T位点基因型病人临床特征、治疗后血清同型半胱氨酸(Hcy)水平变化及疗效,分析MTHFR C677T位点T等位基因对病人的影响。结果:120例病人中MTHFR C677T位点CC、CT及TT基因型病人分别为27例(22.50%)、56例(46.67%)和37例(30.83%),TT基因型病人入院时美国国立卫生院卒中量表(NIHSS)评分、大脑中动脉(MCA)狭窄占比均高于CC基因型和CT基因型(P<0.05)。治疗3个月后,不同MTHFR C677T位点基因型病人血清Hcy水平均较治疗前降低,TT基因型病人Hcy水平下降程度低于CC基因型和CT基因型(P<0.05)。TT基因型病人脑卒中治疗总有效率为72.97%,低于CC基因型病...     

MTHFR基因多态性及Hcy与房颤伴卒中的关系

目的探讨MTHFR基因突变引起Hcy水平升高与中国人种房颤对缺血性卒中的发生是否存在相互关系。方法纳入非瓣膜性房颤和房颤伴缺血性卒中的患者及正常对照组，采用PCR——RFLP的方法研究MTHFR基因677位点上C／T碱基的突变情况。两组计量资料用t检验，多组计量资料用方差分析进行整体比较。结果（1）房颤、房颤伴卒中患者MTHFR基因多态性与血浆Hcy有关，1Tr型Hcy水平（21．38±18．75μmoVL）明显高于CT（14．46±4．70μmol／L），CC（14．33±5．09μmol/L）型；（2）房颤伴卒中组血浆Hcy水平（18．15±13．74μmol/L）较房颤组（13．76±5．12μmol/L）升高明显。结论（1）房颤伴卒中患者血浆Hcy水平明显升高，高Hcy水平可能是非瓣膜性房颤发生卒中的危险因素；（2）MTHFR基因C677T位点突变纯合基因型TT型较CT基因型、CC基因型血浆Hcy升高明显，示TT基因型MTHFR酶活性最低；（3）MTHFR基因C677T位点多态性与房颤伴卒中无关。     

2型糖尿病合并脑梗塞患者的MTHFR基因、eNOS基因多态性位点的联合研究

目的探讨N5,10-亚甲基四氢叶酸还原酶（MTHFR）基因C677T位点、内皮型一氧化氮合酶（eNOS）基因G894T位点与2型糖尿病合并脑梗塞的关系。方法采用Sequenom系统检测内蒙古地区汉族健康对照组65人、2型糖尿病患者34例、2型糖尿病合并脑梗塞患者42例的MTHFR、eNOS基因型。结果（1）eNOS基因G894T位点2型糖尿病合并脑梗组TT基因型频率、T等位基因频率与对照组比较差异有显著性（P〈0．01,P〈0．01）;2型糖尿病合并脑梗组T等位基因频率与糖尿病组比较差异有显著性（P〈0．05）,（2）MTHFR基因C677T位点的TT基因型与eNOS基因G894T位点的TT基因型在2型糖尿病人群患脑梗塞方面具有协同作用（P〈0．05）。结论MTHFR基因C677T位点和eNOS基因G894T位点变异增加糖尿病患者发生脑梗的危险性,可能是糖尿病患者发生脑梗塞的遗传易感基因。     

MTHFR基因多态性与河南中部地区汉族人群急性冠脉综合征发生的关联性研究

目的探讨5,10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性与河南中部地区汉族人群急性冠脉综合征(ACS)发生的关联性。方法招募河南中部地区汉族ACS患者280例作为观察组,选取同期行健康体检的河南中部地区汉族健康受试者286名作为对照组。采用荧光染色原位杂交技术检测两组MTHFR基因C677T、A1298C位点基因型,比较两组受试者各基因型及等位基因分布的差异,采用二元Logistic回归分析MTHFR基因多态性与ACS发生的关联性。结果两组各基因型分布频率均符合Hardy-Weinberg平衡(P0.05)。对照组MTHFR C677T位点CC、CT、TT型分布频率分别为31.82%、47.90%、20.28%,MTHFR A1298C位点AA、AC、CC型分布频率分别为73.78%、21.68%、4.54%;观察组MTHFR C677T位点CC、CT、TT型分布频率分别为16.43%、40.71%、42.86%,MTHFR A1298C位点AA、AC、CC型分布频率分别为69.29%、27.14%、3.57%。两组受试者MTHFR C677T各基因型分布频率及等位基因频率比较差异有统计学意义(P0.05),而MTHFR A1298C各基因型分布频率及等位基因频率比较差异无统计学意义(P0.05)。二元Logistic回归分析显示,MTHFR C677T基因型是ACS发生的影响因素(P0.05),以TT型为参照,CC型发生ACS的可能性是TT型的24.4%,CT型发生ACS的可能性是TT型的40.2%。结论 MTHFR基因多态性与河南中部地区汉族人群ACS发生有关,其中C677T位点突变可能是ACS发生的影响因素,而A1298C位点基因多态性与ACS发生的关联性较低。     

MTHFR基因多态性与脑卒中的相关性

目的探讨河南豫北地区汉族脑卒中人群中N5,N10亚甲基四氢叶酸还原酶(MTHFR)基因C677T基因多态性。方法应用聚合酶链反应限制性片段长度多态性技术对151例脑卒中患者和151名健康对照人群进行HFR/C677T基因多态性分析,并对MTHFR/C677 T位点进行单倍型分析;同时检测两组同型半胱氨酸(Hcy)水平。结果两组FR/C677T基因型和等位基因频率有显著差异(P0.05),脑卒中组Hcy水平明显高于对照组(P0.05)。结论 MTHFR T/T基因型可能与脑卒中相关。     

Hyperhomocysteinemia increases the risk of venous thrombosis independent of the C677T mutation of the methylenetetrahydrofolate reductase gene in selected Brazilian patients.

Fasting total homocysteine (tHcy) and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation were evaluated in 91 patients with venous thromboembolism and without acquired thrombophilia, and in 91 age-matched and sex-matched controls. Hyperhomocysteinemia was detected in 11 patients (12.1%) and in two controls (2.2%), yielding an odds ratio (OR) for venous thrombosis of 6.1 [95% confidence interval (CI), 1.3-28.4]. After excluding 21 patients and four controls with other known genetic risk factors for venous thrombosis, the OR was not substantially changed (7.0; 95% CI, 1.5-33.1). The prevalence of the MTHFR 677TT genotype was not significantly different in patients (9.9%) and in controls (5.5%), with an OR for venous thrombosis of 1.8 (95% CI, 0.6-5.8). Subjects with the MTHFR 677TT genotype showed higher levels of tHcy compared with the 677CC genotype in patients (P = 0.010) and in controls (P = 0.030). In conclusion, we found that fasting hyperhomocysteinemia is a risk factor for venous thrombosis in patients without known acquired thrombophilia and other genetic risk factors for venous thrombosis. Although tHcy levels are significantly higher in those homozygous for the MTHFR C677T mutation, this genotype does not increase the thrombotic risk in our study population.     

MTHFR C677T polymorphism and its relation to ischemic stroke in the Black Sea Turkish population

The MTHFR C677T mutation has been shown to be associated with venous thrombosis. The role of this mutation in ischemic stroke is unclear. We investigated whether the MTHFR mutation is a risk factor for patients with ischemic stroke in the Black Sea Turkish population or not. We analyzed 30 patients (19 male, 11 female) [median age: 50 years (range: 28-78)] with ischemic stroke who had no known predisposition factors for stroke and 242 (182 male, 60 female) healthy controls [median age: 42 years (range: 18-65)]. Detection of the MTHFR C677T mutation was performed by using commercially available allele-specific PCR-ELISA kits. Prevalence of the MTHFR C677T genotype was 49.1% (CT, 45.8%; TT, 3.3%) in controls and 50% (CT, 43.3%; TT, 6.6%) in patients [OR: 1.03, 95% CI (0.45-2.35]). The prevalence of homozygous gene mutation for MTHFR was higher among patients with stroke than control subjects, but this difference was not statistically significant. The MTHFR gene mutation is not a risk factor for ischemic stroke formation in patients from the Black Sea region in Turkey.     

亚甲基四氢叶酸还原酶基因多态性与糖尿病微血管并发症相关性研究

目的：探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与中国人2型糖尿病微血管并发症的关系。方法：运用PCR—RFLP检测263例中国人(206例为2型糖尿病，其中148例合并肾病或视网膜病变，57例为正常对照组)MTHFR基因C677T位碱其突变，比较各组间等位基因频率和基因型频率。结果：(1)同时合并肾病和视网膜病变的2型糖尿病组与无微血管并发症的2型糖尿病组及正常对照组相比，TT基因型频率显著增加，突变等位基因T频率也明显升高。(2)2型糖尿病合并肾病组TT基因型频率及T等位基因频率明显高于不伴有肾病的2型糖尿病组及正常对照组。(3)2型糖尿病合并视网膜病组与无视网膜病的2型糖尿病及正常对照组相比，TT基因型频率及T等位基因频率明显升高。结论：MTHFR基因C677T碱基突变是促进中国人2型糖尿病患者并发微血管并发症的危险因子，突变T等位基因是糖尿病微血管并发症的易感基因。     

Methylenetetrahydrofolate reductase gene polymorphisms in essential hypertension relation: with the development of hypertensive end-stage renal disease

BACKGROUND: The pathogenesis of hypertensive nephropathy is multifactoral and in addition to BP, other factors contribute to the development of this renal pathology and its progression to end-stage renal disease. These include genetic predisposition and increased pleasure level of homocysteine-intermediate protein catabolism product known to induce kidney injury. The 677C --> T polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene is associated with elevated homocysteine level in the general population, and therefore it has been hypothesized to be a risk factor for the development of renal failure in the course of essential hypertension. METHODS: In this case-control, cross-sectional study the frequency of the MTHFR 677C --> T and the 1298A --> C polymorphism was compared between patients with hypertension-related chronic renal failure (n = 90), patients with essential hypertension without kidney injury (n = 90), and healthy individuals (n = 90) who were matched for age and gender. In addition, the influence of these polymorphisms on homocysteine concentration in individuals with essential hypertension was examined. RESULTS: The frequency of the MTHFR 677 TT genotype did not differ between groups (4.5%, 12.3%, and 11.1%, respectively). Patients with hypertension and the 677TT genotype showed significantly higher homocysteine levels as compared to individuals having CC and CT. In the multivariate correlation analysis the MTHFR 677TT genotype (P < .01; beta = 0.27), age (P < .001; beta = 0.33), and body mass index (P < .01; beta = 0.3) were independent predictors for total homocysteine level. CONCLUSIONS: Plasma homocysteine levels in individuals with essential hypertension is affected by the MTHFR 677C --> T polymorphism. However, we did not prove the hypothesis that MTHFR 677C --> T influences the risk of development of renal failure in the course of hypertension.     

The MTHFR CT polymorphism confers a high risk for stroke in both homozygous and heterozygous T allele carriers with Type 2 diabetes.

OBJECTIVE: Individuals with Type 2 diabetes are at increased risk of stroke. Plasma homocysteine (tHcy) is an independent risk factor for cardiovascular (CV) disease. The methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism (thermolabile variant C(677)T) is associated with CV risk, partly as a result of increased Hcy, especially in homozygous subjects. AIM: To relate the occurrence of the MTHFR polymorphism with stroke prevalence by examining allelic frequency and genotype distribution in 165 subjects with Type 2 diabetes studied for the presence of thermolabile C(677)T MTHFR mutation. RESULTS: Mean age was 67.7 years, and tHcy 18.2 micromol/l. T allele frequency was 38.5%. MTHFR genotypes were: normal (CC) 40%; heterozygous (CT) 43%; homozygous (TT) 17%. Serum levels of folic acid and B12 vitamin were within normal limits. Stroke prevalence was 14%. Sixty-four per cent of stroke-free subjects had the normal C allele vs. 46% in stroke subjects. The frequencies of genotypes (CC-CT-TT) were (%): 44-41-15 in stroke-free vs. 17-57-26 in stroke patients. Coronary (CAD) and peripheral artery disease (PAD) were common in all groups, with no differences according to genotypes. Stroke prevalence was markedly higher in genotypes CT and TT (18 and 21%) compared with CC (6%). Mean tHcy levels were higher in TT subjects. CONCLUSION: The allelic frequency of C(677)T MTHFR mutation in Type 2 diabetes subjects with stroke is markedly different from that of subjects without stroke. Genotypic characteristics suggest that C(677)T MTHFR mutation confers a higher risk for stroke to both homozygous and heterozygous T allele carriers that cannot be ascribed solely to raised tHcy and/or lower folate status in CT subjects, nor to phenotypic expression of conventional risk factors for stroke. The impact of the MTHFR polymorphism on stroke may result from T allele-linked deleterious effects, or C allele-linked protection. Confirmatory studies are warranted, as this cohort was not randomly selected, and a type 1 error cannot be ruled out.     

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 677 C-->T mutation and coronary heart disease risk in UK Indian Asians

Plasma homocysteine concentrations are elevated in UK Indian Asians and may contribute to twice as many coronary heart disease (CHD) deaths in this group compared with European whites. The mechanisms underlying elevated homocysteine concentrations among Indian Asians are not well understood. In this study, we have investigated the extent to which the methylenetetrahydrofolate reductase (MTHFR) 677 C-->T mutation accounts for elevated plasma homocysteine and increased CHD risk in Indian Asians compared with European whites. We investigated 454 male cases (with myocardial infarction or angiographically proven CHD: 224 Indian Asians, 230 European whites) and 805 healthy male controls (381 Indian Asians, 424 European whites). Fasting homocysteine concentrations, MTHFR 677 C-->T genotype, and conventional CHD risk factors were measured. The prevalence of homozygous MTHFR 677T in Indian Asian controls was less than one third that in European white controls (3.1% versus 9. 7%, P<0.001). In Indian Asians, the TT MTHFR genotype was not associated with homocysteine concentrations and was not present in any of the Asian controls with hyperhomocysteinemia (>15 micromol/L). In contrast, among European whites, the TT MTHFR genotype was strongly related to elevated plasma homocysteine concentrations and was found in 27% of the European controls with hyperhomocysteinemia. Elevated homocysteine in Indian Asian compared with European white controls was accounted for by their reduced levels of B vitamins but not by the MTHFR 677T genotype. However, neither the TT MTHFR genotype nor B vitamin levels explained the elevated homocysteine concentrations in CHD cases compared with controls. TT MTHFR was not a risk factor for early-onset CHD in Indian Asians (odds ratio, 0.5; 95% confidence interval, 0.1 to 2.4; P=0.39), unlike in European whites (odds ratio, 2.1; 95% confidence interval, 1.1 to 4. 1; P=0.02). We conclude that the MTHFR 677T: mutation does not contribute to elevated plasma homocysteine concentrations or increased CHD risk in Indian Asians compared with European whites. Our results suggest that novel genetic defects and/or environmental factors influence homocysteine metabolism in Indian Asians residing in the United Kingdom.     

绝经后妇女MTHFR基因多态性位点联合作用与骨质疏松易感性的相关性分析

目的研究5,10亚甲基四氢叶酸还原酶(methylene tetrahydrofolate reductase,MTHFR)的2个多态性位点rs1801131 A1298C和rs1801133 C677T的联合作用与苏州地区绝经后妇女骨质疏松遗传易感性的相关性。方法对从苏州市城区随机抽取的261例45~70岁绝经后妇女进行流行病学调查、基础资料测量及桡骨远端骨密度测定,利用荧光定量PCR技术(TaqMan)进行基因分型。应用SAS 9.1.3统计软件进行统计分析,PHASE 2.0软件进行单倍型分析,应用广义多因子降维法(GMDR软件,version 0.7)检测位点-位点、位点-环境之间的联合作用。结果调整年龄、体质量指数(BMI)、腰臀比(WHR)及产次后,MTHFR基因rs1801133(C→T)的位点变异与骨质疏松的发生成正关联。与野生型rs1801133 CC基因型相比,突变纯合型rs1801133 TT及CT/TT型可以显著增加骨质疏松的发生风险[调整OR=2.63,2.37;95%CI=(1.20~5.77),(1.16~4.87)]。经1000次置换检验(Permutation test)方法校正后,该位点的基因型频率分布在病例组与对照组间仍存在统计学差异。单倍型分析结果显示,与最常见的单倍型CC相比,含突变等位基因rs1801131 A的单倍型AC可以显著降低绝经后妇女骨质疏松的患病风险[调整OR=0.60;95%CI=(0.39~0.90)]。广义多因子降维法结果显示,模型A1 A2(rs1801131,rs1801133)为最佳模型(交叉验证一致性10/10,P=0.0107)。结论 MTHFR基因rs1801133位点多态性与苏州地区绝经后妇女骨质疏松的发病风险存在明显关联;rs1801131位点可能与rs1801133位点产生联合作用,共同影响绝经后妇女骨质疏松的发生风险。     

Prevalence of factor V Leiden, prothrombin G20210A, and MTHFR G677A among 594 thrombotic Jordanian patients.

Venous thromboembolism develops as the result of multiple interactions between non-genetic and genetic risk factors. In order to estimate the frequency of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in Jordanian thrombotic patients, we studied 594 patients admitted to the King Hussein Medical Center for thrombophilia assessment. Polymerase chain reaction detected 25.7% (20.7% heterozygous, 5% homozygous), 6% (5.8% heterozygous, 0.2% homozygous) and 31.7% (25% heterozygous, 6.7% homozygous) for factor V Leiden, prothrombin G20210A and MTHFR C677T mutations, respectively. A one-stage clotting assay was used to measure prothrombin activity. None of the prothrombin G20210A mutant patients had high prothrombin activity. The high prevalence found among our study group of factor V Leiden and prothrombin G20210A confirms the importance of thrombophilia screening for patients with venous thrombosis with family history and those with additional risk factors. On the contrary, the high prevalence of the MTHFR C677T mutation among arterial thrombosis patients shows its importance in screening in arterial thrombosis patients. These results, which are close to the prevalence found by other studies in the region, suggests that the Eastern Mediterranean region is probably the area of origin of these mutations, especially factor V Leiden. The knowledge of these frequencies in the Middle East region through population-based studies will contribute to a better understanding of the interaction between genetic and environmental risk factors underlying the mentioned mutations.