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。     

同型半胱氨酸及相关酶基因多态性与糖尿病大血管病变的研究进展

同型半胱氨酸(HCy)是蛋氨酸代谢过程中产生的一种含硫氨基酸。研究表明，血浆同型半胱氨酸水平升高能引起血管损伤，是心脑血管疾病的独立危险因素。亚甲基四氢叶酸还原酶和胱硫醚-B合成酶与HCy关系密切，该基因突变可能是高HCy产生和诱发疾病的一个重要原因。HCy相关酶基因多态性通过改变表达产物的活性，参与糖尿病大血管病变的发生、发展。     

同型半胱氨酸的代谢及相关酶基因多态性

同型半胱氨酸是蛋氨酸代谢过程中形成的一种含硫氨基酸。研究认为它与多种疾病相关。高同型半胱氨酸血症的具体发病机制还不清楚。近年来的研究发现参与它代谢的酶的基因多态性在其发生中起重要作用。本文将就同型半胱氨酸的代谢和参与它代谢过程的酶基因多态性的研究进展作一综述。     

同型半胱氨酸及其代谢酶基因多态性与动脉粥样硬化研究近况

同型半胱氨酸 (homocysteine ,Hcy)是人们较为关注的一个动脉粥样硬化的新候选危险因素。在对血Hcy水平与动脉粥样硬化关系研究不断深入的同时 ,Hcy代谢酶基因多态性的研究也越来越受到重视 ,现对此综述如下。　　一、Hcy及其代谢　　 (一 )Hcy的代谢 :Hcy是一种含硫氨基酸 ,通过转甲基及转硫基两条途径进行代谢。转甲基途径主要以 5 甲基四氢叶酸为甲基供体 ,以VitB12为辅酶 ,经蛋氨酸合成酶(MS)催化形成四氢叶酸 (FH4 )和蛋氨酸 (Met) ,5 甲基四氢叶酸的量与亚甲基四氢叶酸还原酶 (MTHFR)的活性有关 ,MS的辅酶VitB12 (钴胺素 )…     

同型半胱氨酸及其代谢酶基因多态性与动脉粥样硬化和脑梗死

高同型半胱氨酸血症是近年来提出的动脉粥样硬化及其血管并发症新的独立危险因素。造成血浆同型半胱氨酸水平升高的因素主要有营养因素和同型半胱氨酸代谢酶基因多态性 ,后者是否为动脉粥样硬化和脑梗死的基因危险因素目前还存在争论。对高同型半胱氨酸血症的治疗也进行了一些研究。     

同型半胱氨酸及其代谢酶基因多态性与动脉粥样硬化和脑梗死

高同型半胱氨酸血症是近年来提出的动脉粥样硬化及其血管并发症新的独立危险因素。造成血浆同型半胱氨酸水平升高的因素主要有营养因素和同型半胱氨酸代谢酶基因多态性，后者是否为动脉粥样硬化和脑梗死的基因危险因素目前还存在争论。对高同型半胱氨酸血症的治疗也进行了一些研究。     

同型半胱氨酸及其相关酶基因多态性与糖尿病神经病变的关系

同型半胱氨酸（Hcy)是一种含硫氨基酸，属于蛋氨酸循环的中间产物。近年的研究证明，该物质是心、脑血管疾病的独立危险因素。亚甲基四氢叶酸还原酶基因突变可能是高Hcy血症产生和诱发疾病的一个重要原因。Hcy与糖尿病大血管并发症的关系已得到证实，Hcy与糖尿病神经并发症的关系研究较少。     

2型糖尿病合并冠心病患者血清同型半胱氨酸水平的研究

糖尿病患者并发冠心病是非糖尿病患者的 2～ 6倍。高血糖和动脉粥样硬化之间存在着共同的遗传和生化代谢基础 ,Ｘ综合征是它们发生的共同土壤。研究结果显示 ,高同型半胱氨酸血症是冠心病的一个独立危险因素〔1〕。它导致冠心病的机制复杂 ,糖尿病患者由于胰岛素缺乏或作用减弱影响血糖、血脂代谢 ,同时也可能影响同型半胱氨酸的分解代谢。而肥胖、高血糖、脂质异常均可造成胰岛素代谢紊乱。同型半胱氨酸 (Ｈｃｙ)增高又可打破其原来与胰岛素分泌之间的平衡。本研究主要观察 2型糖尿病合并冠心病患者血清同型半胱氨酸水平的变化。一、对象和…     

单纯收缩期高血压患者同型半胱氨酸代谢关键酶基因多态性相关因子研究

目的　研究同型半胱氨酸代谢关键酶亚甲基 4 氢叶酸还原酶 (MTHFR)及胱硫醚 β 合成酶 (CBS)基因多态性及其代谢相关因子在收缩期高血压 (ISH)发病中的作用 ,寻找ISH的易感基因及中间表型。方法　从天津高血压防治区选取ISH患者 5 5例 ,对照组 46例 ,应用分子生物学方法对其进行MTHFRC6 77,CBSG919,T833,C341位点基因多态性检测 ,并同时测定血中同型半胱氨酸(Hcy)、叶酸、维生素B6 、维生素B1 2 浓度 ,并对结果进行相关性分析。结果　ISH组中MTHFR及CBS基因构成与对照组不同存在统计学差异 (P <0 0 5 )。ISH组中MTHFRT等位基因为 6 9 1% ,其发生率高于对照组 (P <0 0 1) ;CBS阳性等位基因发生率为 15 2 % ,与对照组不同。ISH组Hcy水平 [( 17 70± 8 5 0 ) μmol L]高于对照组 [( 10 6 5± 3 10 ) μmol L](P <0 0 5 )。而叶酸、维生素B6 、维生素B1 2 浓度与对照组相比明显降低 (P <0 0 5 )。ISH组中高同型半胱氨酸血症的发生率高于对照组 ,具有统计学差异 (P <0 0 5 ) ,ISH组及对照组三种基因型血浆Hcy水平的改变存在着相同的趋势 ,即突变型高于杂合型与野生型。但血压升高的水平与Hcy浓度之间并无同向性变化。Hcy水平的增高可以增加ISH的发病 ,叶酸在ISH的发病中具有负性作用。结论　Hcy代谢     

胆固醇酯转运蛋白基因多态性与2型糖尿病合并冠心病的关系

以PCR-RFLP检测胆固醇酯转运蛋白(CETP)基因TagⅠB多态性。CETP基因第1内含子TagⅠ B2B2基因型可能是糖尿病患者冠心病发生的保护性基因型。     

MTHFR C677T基因多态性对稳定性冠心病患者叶酸降低同型半胱氨酸治疗的影响

目的探讨MTHFR C677T基因多态性对河南中部汉族稳定性冠状动脉粥样硬化性心脏病(冠心病)患者叶酸降低同型半胱氨酸(Hcy)治疗的影响。方法连续入选2018年4月至2018年9月于许昌市中心医院心血管内科住院的冠心病患者362例,依据MTHFR C677T基因检测结果分为A(CC型)、B(CT型)、C(TT型)三组,三组患者均在冠心病二级预防治疗的基础之上给予叶酸片降低Hcy治疗。记录患者应用叶酸治疗前、治疗后1个月、3个月血浆Hcy的变化,计算三组治疗3个月时降低Hcy治疗有效率,并对影响降低Hcy治疗的因素进行二元logistic回归分析。结果A、B、C三组分别有81例(22.4%)、169例(46.7%)和112例(30.9%)患者,三组治疗前血浆Hcy水平差异无统计学意义(P>0.05);三组治疗1个月和3个月血浆Hcy水平均低于治疗前,且A组治疗1个月时血浆Hcy水平低于B组和C组,差异均有统计学意义(P<0.05)。A组治疗有效率高于B组和C组,差异有统计学意义(P<0.05)。二元logistic回归分析显示,CC型患者降低Hcy治疗有效的可能是TT型患者的2.626倍,有熬夜史患者降低Hcy治疗有效的可能是无熬夜史患者的44.3%。结论MTHFR C677T基因多态性对稳定性冠心病患者叶酸降低Hcy治疗有影响,患者在降低Hcy治疗时应改变熬夜习惯。     

Effect of polymorphisms on key enzymes in homocysteine metabolism, on plasma homocysteine level and on coronary artery-disease risk in a Tunisian population

BACKGROUND: Hyperhomocysteinemia is known as an independent-risk factor for coronary-artery disease (CAD). However, the effect of homocystein metabolic enzymes polymorphisms on CAD is still controversed. We investigated the relation between homocystein metabolic key enzymes polymorphisms, homocystenemia and coronary stenosis in a Tunisian population. METHODS: Samples were collected from 251 CAD patients documented by angiography. Genotyping were performed for C677T methylene-tetrahydrofolate reductase (MTHFR), A2756G methionine-synthase (MS) and 844ins 68 cystathionine-beta-synthase (CBS). We measured fasting plasma tHcy, folate and vitamin B12. RESULTS: There was significant increase in homocysteinemia for homozygous genotypes of C677T MTHFR (p<0.001) and A2756G MS (p=0.01), but not for 844ins68 CBS (p=0.105). Potential confounders adjusted odds-ratios for significant coronary stenosis, associated with MTHFR TT, MS GG and CBS insertion, were respectively 1.78 (p=0.041); 2.33 (p=0.036) and 0.87 (p=0.823). The effect of mutated MTHFR genotype was more pronounced on homocysteinemia (21.4+/-9.1mumol/L; p<0.001) and coronary stenosis (OR=2.73; p=0.033) at low folatemia (相似文献   

亚甲基四氢叶酸还原酶基因C677T多态性与HBV感染后疾病转归的关系

目的:探讨MTHFR C677T多态性对HBV感染后疾病转归的关系. 方法:采用TaqMan SNP基因分型和基因测序的方法检测152例健康对照人群、161例感染HBV后自愈者、173例慢性乙型肝炎患者、138例乙型肝炎肝硬化患者以及181例HBV相关性肝癌患者的MTHFR基因C677T位点的基因型及等位基因的分布及其差异. 结果:805例研究对象的基因型分布为CT基因型占47.09%、TT占30.43%、CC占22.48%;等位基因频率:C为46.02%,T为53.98%,此结果明显不同于以往报道.等位基因和基因型分布在各肝病组无统计学差异.分析不同性别在各组中的分布特征表明,男性患者TT在各组中显示风险降低,特别在肝硬化组TT和CT的OR值最低(与自愈组比较:0.675,95%CI:0.308-1.479;0.510,95%CI:0.248-1.050);而在女性的自愈、慢乙型肝炎和肝硬化组,TT和CT显示风险度增加,特别在肝硬化组OR值最高(与自愈组比较:3.542,95%CI:0.885-14.171;3.167,95%CI:0.821-12.211),具有统计学差异(P=0.022).同时,在女性肝癌组却显示风险度降低(0.638,95%CI:0.213-1.904;0.500,95%CI:0.175-1.432). 结论:本研究显示MTHFR C677T多态性在中国天津汉族人中显示了较高的TT基因型频率,同时提示MTHFR C677T多态性在HBV感染后疾病发展的过程中发挥重要作用.     

The methylenetetrahydrofolate reductase gene C677T polymorphism in patients with homozygous sickle cell disease and stroke

Homozygosity for the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism may cause hyperhomocysteinaemia, a recognized risk factor for stroke, in individuals with folate deficiency. Homozygous sickle cell (SS) disease is associated both with increased demands for folic acid and a tendency to develop stroke. We therefore investigated a possible role of the MTHFR C677T polymorphism in SS disease patients with stroke. Investigation of the frequency of the polymorphism in 48 patients with stroke and in 48 age-, sex- and racially-matched SS controls without stroke failed to reveal a difference between the groups (Fisher exact test, P = 0.99). Homozygosity for the MTHFR C677T polymorphism is unlikely to be a risk factor for stroke in this population with SS disease.     

Total plasma homocysteine and methylenetetrahydrofolate reductase C677T polymorphism in patients with colorectal carcinoma

INTRODUCTION Homocysteine, a sulfur-containing amino acid produced by the adenylation and subsequent demethylation of dietary methionine, is an essential intermediate in folate metabolism. Two enzymes and three vitamins play a key role in the regulation o…     

MTHFR C677T polymorphism: association with lymphoid neoplasm and effect on methotrexate therapy

The aim of this study was to detect the possible role of methylene tetrahydrofolate reductase gene polymorphism (MTHFR C677T) in the pathogenesis of lymphoid neoplasms and to investigate the influence of this polymorphism on methotrexate toxicity in adult ALL patients treated with methotrexate maintenance therapy. There was a statistically significant increase in the risk of non‐Hodgkin lymphoma in patients with CT genotype (OR, 2.9; 95% CI, 1.3–6.3; P = 0.007) and combined CT + TT genotype (OR, 3.2; 95% CI, 1.5–6.6; P = 0.006). While no significant association was found between this polymorphism and ALL risk. The patients with ALL treated with methotrexate during maintenance therapy were observed for signs of toxicity. MTHFR 677C>T polymorphism (CT + TT) was significantly overrepresented among cases with hepatic toxicity (OR = 15.6; 95% CI, 2.6–81.3; P = 0.001). In addition, they were overrepresented among cases with mucositis, anemia, thrombocytopenia, and leukopenia. However, it did not reach statistical significance level. Further studies on larger number of subjects are necessary. Additional studies on the role of MTHFR gene polymorphism with environment (folate intake) interaction are needed to confirm the role of these genetic polymorphisms.     

MTHFR C677T基因多态性与冠心病患者同型半胱氨酸及冠脉狭窄程度的相关性

[摘 要] 目的 探讨MTHFR C677T基因多态性与河南中部汉族冠心病（CHD）患者同型半胱氨酸(Hcy)及冠脉狭窄程度的相关性。方法 应用荧光染色原位杂交技术对河南中部汉族352例CHD患者和340例非CHD对照者进行MTHFR C677T基因多态性检测,并比较两组不同基因型之间Hcy水平的差异。采用Gensini评分系统评价CHD患者的冠脉狭窄程度,多元线性回归分析法探讨MTHFR C677T基因多态性以及其他因素与Gensini得分之间的相关性。结果 非CHD组MTHFR C677T 基因CC、CT、TT 型例数及分布频率分别为113(33.2％)、159(46.8％)、68(20％),CHD组MTHFR C677T位点CC、CT、TT型例数及分布频率分别为85(24.1％)、157(44.6％)、110(31.3％)。两组受试者各基因型分布频率均符合Hardy-Weinberg 平衡（P＞0.05）。两组受试者MTHFR C677T各基因型分布频率及等位基因频率比较,差异均有统计学意义（P＜0.001）。CHD组血清Hcy水平、高血压、糖尿病患病率分别为（23.1±8.7）、27.8%和16.8%,均高于非CHD组的（18.6±7.4）、10.6%和6.2%,差异均有统计学意义（P <0.05）。两组不同基因型之间血清Hcy水平差异有统计学意义（P <0.05）。多元线性回归分析结果显示,MTHFR C677T基因多态性与Gensini得分的相关性无统计学意义（β=-0.16,95%CI：-0.21～0.18,P=0.785）。结论MTHFR C677T基因多态性影响Hcy水平,但与CHD患者冠脉狭窄程度无明显相关性。     

Methylenetetrahydrofolate reductase C677T polymorphism in adult patients with lymphoproliferative disorders and its effect on chemotherapy

Methylenetetrahydrofolate reductase (MTHFR) is one of the most critical enzyme in folic acid metabolism, and it converts 5,10-MTHF to 5-MTHF. 5,10-MTHF is required for conversion of uridilate to thymidylate. On the other side, MTHFR enzyme causes methylation of homocysteine into methionine, leading to methylation of DNA. Chemotherapeutic agents have different effects, but DNA is the target for most of them. Because folate is the cornerstone in DNA synthesis, we analysed herein if the polymorphisms in MTHFR gene can alter the susceptibility of lymphoproliferative disease risk and if it has an effect on chemotherapy response. One hundred fifty-six patients with lymphoid malignancies and 82 healthy controls were included into the study. Neither gene frequencies nor allel frequencies were found to increase lymphoproliferative disease risk significantly in both overall group and subgroups. Although it was not statistically significant, we found a 2.7-fold increased risk in acute lymphocytic leukaemia (ALL)/Burkitt lymphoma patients with TT genotype [odds ratio (OR), 2.7; 95% confidence interval (CI), 0.88–8.2] than CC genotype but a 1.7-fold decreased risk with TT genotype in diffuse large B-cell lymphoma (DLBCL; OR, 0.58; 95% CI, 0.17–1.88) and a 1.8-fold decreased risk in Hodgkin’s lymphoma with TT genotype (OR, 0.55; 95% CI, 0.10–2.87) than CC genotype. The chemotherapy response was analysed in DLBCL, Hodgkin’s lymphoma and ALL/Burkitt’s lymphoma because these patients received standard chemotherapy protocols. No significant difference was detected between responder and non-responders according to MTHFR T677C polymorphism, but the patients who had TT genotype respond 1.75-fold worse than CC (OR, 0.57; 95% CI, 0.07–4.64) in ALL patients (p=0.59), and in DLBCL, CT genotype revealed a 1.8-fold worse response than CC genotype (OR, 0.54; 95% CI, 0.17–1.7), but TT genotype revealed 2.6-fold better response rates than patients with CC genotype (OR, 2.6; 95% CI, 0.26–26.8). As a conclusion, MTHFR C677T polymorphism does not increase the risk of lymphoproliferative disease, and it does not have an effect on chemotherapy response significantly; however, the patients with TT genotype have a slightly increased risk for ALL, and they also respond worse than CC genotype. TT genotype slightly decreases the risk of DLBCL, and the patients have much favorable response rates.     

Livedoid vasculopathy associated with combined prothrombin G20210A and factor V (Leiden) heterozygosity and MTHFR C677T homozygosity

Livedoid vasculopathy (LV) is an occlusive thrombotic disease of lower extremities. A 34-year-old woman presented with 4-year history of recurrent necrotic and painful lesions with violaceous and purpuric border on both legs. Initial treatment with hydroxychloroquine, dapsone and prednisone were unsuccessful. Skin biopsy showed inflammatory infiltrate with epidermal necrosis. Prothrombin G20210A and factor V-Leiden heterozygosity, and MTHFR C677T homozygosity with hyperhomocysteinemia were confirmed. LV diagnosis was made; acetylsalicylic acid, folic acid, vitamin B12, and prednisone treatement resulted in complete healing. This is the first report on coexistence of prothrombin G20210A, factor V-Leiden, and homozygous MTHFR C677T with hyperhomocysteinemia in LV.