亚甲基四氢叶酸还原酶基因C677T多态与结直肠癌遗传易感性的相关性

目的:探讨亚甲基四氢叶酸还原酶基因(MTHFR)C677T多态与结直肠癌(CRC)遗传易感性的关系.方法:采用TaqMan方法检测CRC 449例与对照672例的MTHFR C677T的基因型分布及差异.以非条件Logistic回归法计算表示相对危险度的比值比(OR)及其95%可信区间(CI).OR值均经性别、年龄、吸烟、饮酒、体质量指数和一级亲属CRC家族史等因素校正.结果:CRC组677T等位基因频率显著低于对照组,其为CRC发生的保护因素(OR:0.70,95%CI:0.58-0.83,P<0.01).与CC纯合子相比,CT杂合子的CRC风险显著降低至0.73倍(95%CI:0.56-0.95,P<0.05),而TT纯合子的CRC风险进一步降至0.47倍(95%CI:0.33-0.68,P<0.01).在非饮酒人群中,C677T的CRC风险保护效应略有增强;而在饮酒人群中,CT和TT基因型携带者的CRC发病风险虽仍低于CC基因型携带者,但差异无统计学意义.在CRC人群中,荷大肿瘤(最大直径>4cm)者携带TT基因型的比例高于荷小肿瘤者(16.3% vs 8.3%,P<0.05);荷黏液腺癌者携带TT基因型的比例高于荷乳头状腺癌及管状腺癌者(22.2% vs 17.1%,10.3%,P=0.084).结论:MTHFR C677T降低CRC发病风险,饮酒可能削弱该多态的CRC风险保护效应.TT基因型可能与CRC肿瘤进展有关.     

甲基四氢叶酸还原酶基因C677T多态性与大肠癌遗传易感性的相关性

目的 探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与大肠癌(CRC)遗传易感性的关系.方法 采用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)分析方法检测120例CRC患者和202例正常对照的MTHFR C677T的基因型分布及差异.结果 与对照组相比,CRC组677T等位基因频率显著降低(OR:0.57,95％ CI:0.40 ～0.81,P=0.002).与CC纯合子相比,TT纯合子的CRC风险显著降低至0.28倍(95％ CI:0.12～0.63,P=0.002) CT杂合子的CRC风险虽降低至0.64倍(95％ CI:0.37～ 1.08,P=0.094),差异无统计学意义.在CRC人群中,MTHFR C677T与肿瘤大小、位置、组织学类型、分化程度、淋巴结转移以及Dukes分期均无显著相关性(P＞0.05).结论 MTHFR 677TT基因型可降低CRC风险;MTHFR C677T基因型与CRC肿瘤特征无相关性.     

亚甲基四氢叶酸还原酶基因多态与脑梗死

血浆同型半胱氨酸 (Ｈｃｙ)浓度升高是动脉粥样硬化的危险因素 ,其代谢的关键酶 5 ,1 0 亚甲基四氢叶酸还原酶(ＭＴＨＦＲ)基因突变引起酶活性下降 ,导致高Ｈｃｙ血症。本组探讨脑梗死患者ＭＴＨＦＲ基因多态性以及Ｈｃｙ和叶酸浓度的关系。1 材料与方法 :病例组 75例 (男 43例 ,女 32例 )。年龄35～ 86岁 ,平均 (60 6± 1 2 1 )岁 ,为急性脑梗死住院患者。对照组 62例 (男 34例 ,女 2 8例 ) ,年龄 30～ 78岁 ,平均 (57 4± 1 1 2 )岁 ,为健康体检者。以上两组均为在黑龙江省生活30年以上汉族人。测定血压、血糖、血脂、血浆叶酸及Ｈｃ…     

亚甲基四氢叶酸还原酶基因多态性与心肌梗死的相关研究

目的 了解亚甲基四氢叶酸还原酶基因Ｃ６７７Ｔ位点突变在中国人群中的频率及其与心肌梗死（心梗）是否相关。方法 选择１５３例住院心梗患及１５６例住院的非心血管病患作为对照,抽取外周静脉血提取ＤＮＡ,同时所有研究对象记录其病史,体检等稞资料及吸烟,饮酒等流行病学资料,应用ＰＣＲ－ＲＦＬＰ进行基因型分析。     

hOGG1基因多态与结直肠癌和肝细胞癌遗传易感性

目的探讨hOGG1基因第326密码子多态（Ser326Cys）与中国人群结直肠癌（CRC）和肝细胞癌（HCC）遗传易感性的关系。方法采用TaqMan方法检测345例CRC与670例对照以及175例HCC与119例对照的hOGG1Ser326Cys基因型分布及差异。结果总体上，hOGG1 Ser326Cys基因型分布在HCC-对照、CRC-对照以及不吸烟的CRC-对照人群间均无显著性差异（P〉O．05）。但在吸烟人群中，326Cys是CRC发生的危险因素（OR=1．58，95％CI=1．14～2．19，P=0．006）；与Ser／Ser基因型及Ser等位基因携带者（Ser／Ser、Ser／Cys基因型）相比，Cys／Cys基因型的CRC风险显著增加至2．40倍（95％CI=1．20～4．78，P=0．013）及2．02倍（95％CI=1．21-3．37，P=0．008）。结论hOGG1Ser326Cys多态可能与HCC发病风险无关，但Cys／Cys基因型增加中国吸烟人群的CRC发病风险。     

亚甲基四氢叶酸还原酶基因C677T突变与高尿酸血症的相关性研究

目的探讨高尿酸血症（HUM）与亚甲基四氢叶酸还原酶（MTHFR）基因C677T突变及高血糖、肥胖和高血压等的相关性。方法从青岛地区糖尿病流行病学调查数据库中，随机选取HUM＋T2DM患者79例、HUM无T2DM患者（HUM组）90例、并选取T2DM无HUA患者（DM组）90例和健康对照（NC）91例。采用聚合酶链反应-限制性片段长度多态性技术检测MTHFR基因突变。结果HUM组和HUM＋T2DM组MTHFR677T等位基因频率分别为46．7％和51．3％，TT基因型频率分别为23．3％和26．6％，两组差异无统计学意义（P〉0．05）；T等位基因和TT基因型频率在NC组和DM组间差异无统计学意义（P〉0．05）；而HUM组和HUM＋T2DM组MTHFR677T等位基因型频率和TT基因型频率均分别高于NC组和DM组（P〈0．005）。CT和TT基因型患者平均血尿酸水平（分别为394．2μmol／L和465．8μmol／L）明显高于CC基因型者（347．3μmol／L）（P〈0．05）。多因素logistic回归分析表明，调整BMI、SBP、TG、TC及饮酒等因素后显示，MTHFR基因型是HUM患病的独立危险因素。结论MTHFR基因C677T突变是青岛地区人群发生HUM的独立危险因素。     

亚甲基四氢叶酸还原酶基因多态性与糖尿病肾病相关性研究

目的：研究亚甲基四氢叶酸还原酶（MTHFR）基因多态性与2型糖尿病肾病的关系。方法：运用聚合酶链反应－限制性片段长度多态性技术（PCR－RFLP）检测85例2型糖尿病患者（其中39例伴糖尿病肾病）及57例正常对照组MTHFR C677T基因型,采用高效液相色谱法测定血浆同型半胱酸水平。结果：糖尿病肾病组MTHFR基因TT纯合基因型,CT杂合基因型及T等位基因频率（分别为38．21％,51．28％,53．85％）均明显高于糖尿病不伴肾病组（分别为19．57％,28．26％,33．70％）及正常对照组（分别为17．54％,28．07％,31．58）,基因型和等位基因频率分布差异均有统计学意义（P＜0．05）,而MTHFR基因该多态性在不伴肾病组与正常对照组之间差异无显著性（P＞0．05）,T等位基因与糖尿病肾病的发生密切相关（OR＝2．30,95％可信区间;1．24－4．26）。糖尿病肾病组,糖尿病不伴肾病组及正常对照组中,MTHFR基因有C677T突变者血浆同型半胱氨酸水平均显著高于无基因突变者。结论：MTHFR基因C677T位碱基突变致血浆同型半胱氨酸水平高是糖尿病肾病发病的重要遗传因素。     

CCND1基因A870G多态与结直肠癌遗传易感性的相关性

目的:探讨CCND1基因A870G多态与上海地区人群结直肠癌(colorectal cancer, CRC)遗传易感性的关系.方法:采用TaqMan MGB探针实时定量PCR法.检测104例CRC与205名对照人群CCND1A870G基因型分布及差异.结果:CRC组和对照组870A等位基因频率分别为60.1%和52.4%,A的CRC发病风险是G的1.40倍(95%CI=0.99-1.97,P=0.057).与GG基因型相比,GA基因型的CRC风险增加至1.99倍(95%CI=0.94-4.20,P=0.070),而AA基因型的CRC风险显著增加至2.46倍(95%CI=1.09-5.56,P=0.031).将GA、AA基因型合并计算,则其CRC发病风险与GG基因型相比呈相似的显著性增加(OR=2.13,95%CI=1.03-4.39,P=0.040).结论:CCND1 870A增加CRC发病风险,可作为这一地区CRC高危人群的筛选指标.     

高血压患者亚甲基四氢叶酸还原酶基因C677T多态性与血脂异常的相关性

目的探讨血浆同型半胱氨酸(Hcy)及其代谢关键酶亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与中国汉族人群原发性高血压患者血脂异常的关系。方法选取原发性高血压患者312例,女性134例,男性178例,平均年龄58.25岁,收集患者基本资料,检测血浆Hcy、血脂、空腹血糖(FBG)、尿酸(UA)等临床生物化学指标。应用Taqman探针技术检测患者MTHFR C677T基因分型。根据2007年中国成人血脂异常防治指南,将入选的312例原发性高血压患者分为血脂异常组194例和血脂正常组118例,同时将血脂异常组分为4个亚组:高胆固醇血症组54例,高甘油三酯血症组53例,混合型高脂血症组59例,低高密度脂蛋白血症组22例,并进行亚组分析。结果血脂异常组体质指数(BMI)、FBG、UA高于血脂正常组(P0.01)。血脂异常组MTHFR C677T的CC、CT、TT三种基因型频率和C、T两种等位基因频率与血脂正常组比较差异无统计学意义(P0.05),血脂异常各亚组之间的基因型频率、等位基因频率差异无统计学意义,与血脂正常组之间差异亦无统计学意义。MTHFR C677T不同基因型间四项血脂水平均无统计学差异,但TT基因型者Hcy水平高于CT、CC基因型者(P0.05),而CT基因型者Hcy水平与CC基因型者比较差异无统计学意义(P0.05)。高密度脂蛋白胆固醇(HDLC)水平与Hcy水平呈负相关(r=-0.116,P0.05),但是在校正了年龄、BMI、UA、FBG后此相关性消失;总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)水平与Hcy水平无相关性(P0.05)。Logistic回归分析显示,在校正了BMI、FBG、UA后基因型与血脂异常无相关性(P0.05)。结论在原发性高血压患者中MTHFR C677T基因多态性与血脂异常无关联,而与Hcy呈显著相关。血脂异常与FBG、UA、BMI有关,而与Hcy无关,但HDLC与血浆Hcy水平呈负相关。     

亚甲基四氢叶酸还原酶C677T基因多态性与肺癌易感性的关系

肺癌在全世界癌症死因中居首位,但其发病机制迄今尚未完全明确.既往文献报道与肺癌发病有关的因素包括吸烟、职业因素、环境污染、病毒感染、遗传背景以及肺癌的基因易感性等.新近的研究结果显示,外来化学物质代谢、DNA修复、细胞周期调控以及相关基因多态性可能与肺癌的发生有关[1].     

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。     

热休克蛋白-2基因多态性与肝细胞癌的相关性

肝细胞癌(HCC)是我国的常见恶性消化道肿瘤之一,全球发病率逐年升高,其发生和发展与遗传、免疫和环境等因素相关.热休克蛋白(HSP)70是生物细胞受到高温、感染、炎症和缺血等应激刺激时产生的一组在进化上高度保守的蛋白质,具有广泛的生物学功能,与HCC的发病关系密切.     

Methylenetetrahydrofolate reductase (MTHFR) C677T genetic polymorphism and late infarct-related coronary artery patency after thrombolysis

In patients with acute myocardial infarction (AMI), a persistently occluded infarct-related artery (IRA) is associated with unfavorable prognosis and genetic factors may be contributing factors to thrombolysis failure. One-hundred and one consecutive patients treated with intravenous thrombolysis during AMI were blind-tested for methylenetetrahydrofolate reductase (MTHFR) and circulating homocysteine levels and underwent protocol angiography 14 ± 6 days after the event. IRA was patent in 61 patients and occluded in 40. Overall MTHFR 677TT frequency was 22%. Patients with MTHFR 677TT homozygosis had higher prevalence of occluded IRA (73%) versus those with MTHFR 677CT/CC genotype (30%, P < 0.001); MTHFR 677TT genotype predicted independently the risk of IRA occlusion with a specificity of 90% (odds ratio 3.8, 95% confidence interval 1.1–9.1; P = 0.03). Moreover, patients with occluded IRA and MTHFR 677TT genotype had the highest homocysteine levels (21 ± 7.6 μmol/l vs. ≤14.9 ± 3.8 μmol/l; P = 0.011). In patients with AMI, MTHFR 677TT homozygosis is independently associated with a persistently occluded IRA after thrombolysis. This finding may have pathophysiological and therapeutic implications for recanalization strategies in patients with AMI.     

单核苷酸多态性与原发性肝细胞癌易感性的研究进展

人群特异的癌症遗传性与DNA序列中的多态性变异有关.人类基因组中最常见的序列变异是单个碱基的稳定替换,即单个核苷酸多态性(single nucleotide polymorphism,SNP).人体许多表型、对药物的敏感性或疾病的易感性差异等都可能与SNP相关,已有人将SNP称为第三代遗传标志.原发性肝细胞癌(HCC)某些特定的SNP可以通过改变基因的功能和表达影响个体对HCC的易感性,具体可能在多种途径发挥作用,现就能够影响HCC发病风险的SNP位点综述如下.     

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 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.     

Lack of association between the MTHFR (C677T) polymorphism and atopic disease

Background: Impaired folate metabolism has been suggested as a potential risk factor for the development of asthma and atopic disease. However, there have been conflicting reports on the potential association between atopic disease and a common polymorphism of the methylene‐tetrahydrofolate reductase (MTHFR)‐gene, a well‐known marker of impaired folate metabolism. Objectives: The aim of this study was to investigate the association between the MTHFR (C677T) polymorphism and different outcome variables of asthma and atopic disease. Methods: This study was a population‐based study of 1189 participants aged 15–77 years living in Copenhagen, the Capital of Denmark. Examinations included measurements of specific IgE and skin prick tests against inhalant allergens, metacholine bronchial hyper‐reactivity, and serum eosinophilic cationic protein, and a self‐administered questionnaire about diagnoses and symptoms of allergy and asthma. In addition, participants were genotyped for the MTHFR (C677T) polymorphism. Results: None of the examined outcomes were significantly associated with the MTHFR (C677T) polymorphism. Conclusions: The results of this study using detailed objective markers of atopic disease do not support the hypothesis that impaired folate metabolism as reflected by the MTHFR genotype is involved in the development of atopic disease. Please cite this paper as: Thuesen BH, Husemoen LLN, Fenger M and Linneberg A. Lack of association between the MTHFR (C677T) polymorphism and atopic disease. The Clinical Respiratory Journal 2009; 3: 102–108.