亚甲基四氢叶酸还原酶基因C677T多态性与习惯性流产相关的Meta分析

目的探讨5,10-亚甲基四氢叶酸还原酶（MTHFR）基因C677T位点多态性与习惯性流产易感性关系。方法检索习惯性流产组和对照组MTHFR基因C677T位点多态性的OR值或RR值为效应指标的相关文献,符合入选标准的文献,应用RevMan 5.0软件对各研究结果进行异质性检验和效应值合并,并进行敏感性分析和偏倚评估。结果纳入MTHFR基因C677T位点多态性文献12篇,共计病例1127例,对照1119例,根据异质性检验结果,采用相应的效应模型进行合并分析。结果 MTHFR基因677位点CT、TT、CT＋TT基因型的OR值为1.24（1.02～1.52）、2.20（1.31～3.68）、1.39（1.15～1.67）。各研究的敏感性分析比较稳定,漏斗图形基本对称。亚组分析结果提示亚洲地区CT、TT、TT＋CT基因型的OR值分别为1.41、2.41、1.65,P=0.17、0.02、0.03。而非亚洲地区3种基因型的OR值分别为1.13、1.78、1.24,P=0.40、0.02、0.11。结论 MTHFR基因C677T位点多态性与习惯性流产的发生密切相关。尤其是MTHFR677位点TT、CT＋TT基因型是亚洲人群习惯性流产的危险因素。     

亚甲基四氢叶酸还原酶基因(C677T)多态性研究进展

亚甲基四氢叶酸还原酶 (methylenetetrahydrofolate reductase,MTHFR)在叶酸和同型半胱氨酸代谢、DNA甲基化和 DNA合成等方面起重要作用。 MTHFR基因突变引起酶耐热性和活性降低 ,导致 DNA结构和相应代谢异常 ,引起疾病发生。MTHFR有多种突变类型。本文对 MTHFR C6 77T多态性及其与疾病关系的研究进行了综述     

亚甲基四氢叶酸还原酶基因（C677T）多态性研究进展

亚甲基四氢叶酸还原酶（methylenetrahydrofolate reductase,MTHFR)在叶酸和同型半胱氨酸代谢，DNA甲基化和DNA合成等方面起重要作用，MTHFR基因突变引起酶耐热性和活性降低，导致DNA结构和相应代谢异常，引起疾病发生，MTHFR有多种突变类型，本对MTHFRC677T多态性及其与疾病关系的研究进行了综述。     

亚甲基四氢叶酸还原酶基因多态性及其与疾病的关系

亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase, MTHFR）在叶酸和同型半胱氨酸代谢、DNA甲基化和DNA合成等方面起重要作用。MTHFR基因突变造成酶活性和耐热性降低，导致高半胱氨酸血症和DNA结构异常，从而影响多种疾病的发生。现已发现MTHFR基因多态性与心脑血管疾病、出生缺陷和一些肿瘤等多种疾病存在相关性。     

亚甲基四氢叶酸还原酶基因多态性及临床意义

亚甲基四氢叶酸还原酶基因多态性特别是677 C→T突变可导致MTHFR酶活性下降,使 血浆同型半胱氨酸增高及DNA低甲基化,被认为与多种疾病有关,本文就近年来的有关研究作一综 述。     

脑梗死患者同型半胱氨酸水平与亚甲基四氢叶酸还原酶基因C677T多态相关性研究

目的 研究甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL)、脂蛋白a[LP(a)]、同型半胱氨酸(Hcy)水平及5,10-亚甲基四氢叶酸还原酶(MTHFR) C677T位点基因多态性与脑梗死的相关性.方法 选择2013年1月至2013年11月入住延安大学附属医院的脑梗死患者255例为脑梗死组,以同期在我院体检正常者128例为对照组,分别检测两组血脂四项、Hcy水平及MTHFR C677T基因多态性.结果 脑梗死组患者血清Hcy、TG、TC、LDL、LP(a)水平分别为19.76 ±5.24μmoL/L、1.92±0.39mmol/L、5.05±0.66mmol/L、3.14±0.53mmol/L、305.48±82.83mg/L,均明显高于对照组(P ＜0.001);TT、TC、CC基因型分布频率分别为33.0％、43.1％、23.9％,等位基因T、C频率分别为54.5％、45.5％,与对照组相比,差异均有统计学意义(P＜0.05);脑梗死组各基因型Hcy水平均高于对照组,差异有统计学意义(P＜0.001),其中TT型Hcy浓度最高,CT型次之,CC型最低,差异有统计学意义(P ＜0.001).结论 脑梗死患者Hcy及血脂四项水平均显著增高,MTHFR C677T多态性TT基因型致Hcy水平增高,可能是引发脑梗死的重要遗传因素,血脂四项结合Hcy及MTHFR C677T基因多态性检查可更好的用于脑梗死易感人群筛查.     

变性高效液相色谱检测5,10-亚甲基四氢叶酸还原酶基因677(C/T)多态

目的建立快速、准确的筛查5，10-亚甲基四氢叶酸还原酶基因（methylenetrahydrofolate reduclase gene，MTHFR）677（C／T）多态的方法。方法MTHFR扩增后，应用变性高效液相色谱进行检测，用测序和酶切验证。结果对334名南方汉族人的MTHFR的677（C／T）多态进行了检测，准确率达99％以上，灵敏度高，突变的检出率达100％。CC、CT、TT基因型的频率分别为56．9％、38．3％和4．8％，T、C等位基因的频率分别为23．95％和76．05％。结论变性高效液相色谱法能快速、准确地检测MTHFR的677（C／T）多态。MTHFR的677（C／T）多态存在地区和种族差异。     

亚甲基四氢叶酸还原酶基因多态性与习惯性流产关系研究

目的　探讨广东地区汉族妇女亚甲基四氢叶酸还原酶基因多态性与习惯性流产关系 .方法　采用多聚酶链式反应限制性片段长度多态分析 (PCR -RFLP)的方法 ,对 5 0例习惯性流产和 5 6例正常对照的广东地区汉族妇女进行MTHFR6 77C→T突变检测 .结果　习惯性流产组与正常对照组之间基因型的分布有显著差异 :χ2 =11.0 7,p<0 .0 5 ;但两组间等位基因突变频率无显著差异 :χ2 =2 .0 6 ,p>0 .0 5 .流产组 6 77C→T突变纯合子 ( 2 4 .0 % )较对照组 ( ( 7.1% )明显升高 .等位基因突变频率流产组 ( 2 6 .0 % )较对照组 ( 17.9% )升高 .结论　MTHFR 6 77C→T纯合子突变与习惯性流产有明确的相关关系 .     

亚甲基四氢叶酸还原酶基因C677T突变与冠心病的连锁分析

目的探讨亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase, MTHFR)基因C677T突变是否与冠心病连锁。方法应用传递不平衡检验(transmission/disequilibrium test, TDT)分析了先证者一级亲属中至少有1例冠心病患者的冠心病家系45个,调查了212人。其中完整核心家系、父母一方、双方基因型缺失家系分别为21、2和22个。PCR-RFLP鉴定MTHFR基因C677T位点基因型。结果 23个核心家系经经典TDT分析,杂合子父母传递给患病子女的T等位基因频率未显著偏离50%(P＞0.05);对40个符号要求的同胞组资料的同胞传递不平衡检验(sib transmission/desequilibrium test, STDT)和同胞组不平衡检验(sibship disequilibruium test, SDT)检验均未发现受累子代与非受累子代T等位基因分布差异有显著性(P＞0.05)。结论 MTHFR基因C677T突变与冠心病不连锁,提示该位点可能不是中国人冠心病的遗传易患因子之一。     

昆明地区妊娠期妇女亚甲基四氢叶酸还原酶基因C677T多态性分析

目的 探索昆明地区妊娠期妇女亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性的空间分布特征,为昆明地区出生缺陷防控工作提供参考依据.方法 回顾性分析2019-2020年昆明地区6004例妊娠期妇女亚甲基四氢叶酸还原酶基因C667T多态性检测结果,采用Arc GIS 10.4软件及SPSS 23.0统计学软件进行空...     

MTHFR基因C677T多态性与冠心病患者血浆同型半胱氨酸和叶酸水平相关

目的研究宁夏地区汉族人群5,10-亚甲基四氢叶酸还原酶基因(MTHFR)C677T多态性、同型半胱氨酸水平(Hcy)及叶酸水平与冠心病(CHD)的相关性。方法用病例-对照研究方法、应用限制性片段长度多态性扩增技术(PCR-RFLP)分析宁夏地区汉族202例冠心病患者及199例正常人群MTHFRC677T基因型频率及基因频率的分布特点。荧光偏振免疫分析法测定血浆Hcy水平,化学发光免疫分析法测定血清叶酸、VitB12浓度。结果 (1)病例组与对照组MTHFRC677T基因型频率分别为CC型23.3%vs20.7%、CT型52.3%vs54.5%和TT型24.4%vs24.8%,两组间基因型及等位基因频率分布无差异。(2)冠心病患者组中MTHFR基因C677TCC基因型患者血浆Hcy浓度(10.84μmol/L)较T基因携带者(12.24μmol/L)低(P<0.01)。CC基因型患者血浆叶酸浓度(5.38μg/L)较T基因携带者(3.72μg/L)高(P<0.05)。结论 MTHFRC677T的3种基因型频率在宁夏汉族冠心病患者和正常人群中的分布无统计学意义。MTHFR基因C677T多态性与冠心病的危险因素Hc...     

血管内皮生长因子基因多态性与先天性心脏病相关性的Meta分析

目的 评价血管内皮生长因子（VEGF）等位基因、基因型、基因单倍型多态性与先天性心脏病（CHD）的相关性.方法 检索Cochrane图书馆、Medline、PubMed、EMBASE、中国期刊全文数据库、万方数据库及中国生物医学文献数据库,检索起止时间均为建库至2011年12月,并且对重要文献的参考文献采取手工回溯检索.获取VEGF与CHD相关性的病例对照研究和传递不平衡检验文献.对文献进行质量评价.采用RevMan 5.1.1软件进行异质性检验,根据检验结果选择适当的效应模型进行Meta分析.结果 6篇文献共10项独立研究纳入分析,漏斗图检验存在发表偏倚.Meta分析结果显示：① VEGF C-2578A和G-1154A位点等位基因变异显著增加DiGeorge综合征患者的CHD易感性,OR分别为1.40（95%CI：1.04～1.16）和1.87（95%CI：1.27～2.75）;G-634C位点的等位基因变异显著增加普通病例的CHD易感性,OR=1.29,95%CI：1.02～1.62.② G-1154A位点（AA＋AG）为DiGeorge综合征患者合并CHD的危险因素,OR=2.10,95%CI：1.32～3.34.③单倍型AAG在DiGeorge综合征患者中显著增加CHD易感性,OR=1.82,95%CI：1.31～2.54;单倍型CGC显著降低普通病例CHD风险的保护作用,OR=0.79,95%CI：0.63～0.99.结论 VEGF等位基因、基因型、基因单倍型多态性与CHD易感性存在一定的相关性,且在DiGeorge综合征患者与普通患者间存在差异;在不伴DiGeorge综合征的人群中,特定单倍型（CGC）则有显著降低CHD风险的保护作用,其作用机制尚需进一步明确.     

Lack of association between methylenetetrahydrofolate reductase (MTHFR) C677T and ischaemic heart disease (IHD): family-based association study in a Spanish population

The effect of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, traditionally associated with ischaemic heart disease (IHD), was assessed in a Spanish population. The transmission disequilibrium test (TDT) was used to determine a possible association in a sample of 101 trios of IHD patients. The distribution of MTHFR genotypes was similar in the IHD subjects and the parental group; the TT genotype was present in 14.9% of IHD patients, as compared to 15.2% in the parents. The frequency of the T allele was also similar in IHD cases and parents (39.6% vs. 42.4%; p = 0.649). The TDT confirmed that the observed transmission of the T allele did not deviate significantly from the expected one (chi2 = 0.743; p > 0.4). Our TDT analysis clearly demonstrates a lack of association between the T allele of the C677T mutation in MTHFR and cardiovascular artery disease, both for the general group and for different risk subgroups (smokers, hypertension, male sex, overweight and type A behaviour pattern) in the Spanish population.     

MTHFR基因多态性与老年冠心病及同型半胱氨酸的相关性研究

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）与老年冠心病的相关性。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120例老年冠心病患者（CHD组）和58例健康老年人（对照组）的血浆Hcy浓度及MTHFR基因型。结果两组MTHFR 677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）;CHD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CHD的高危因素。     

Maternal mutation 677C > T in the methylenetetrahydrofolate reductase gene associated with severe brain injury in offspring

A frequent polymorphism in the gene coding for 5,10-methylenetetrahydrofolate reductase is the substitution 677C > T which produces a thermolabile and inefficient enzyme. Homozygosity for the 677C > T allele is the most important determinant of hyperhomocys-teinemia, when folic acid intake is reduced. Most studies on the relationship between the 677C > T variant in the mother and defects in the offspring have focused on neural-tube defects. This study is a retrospective case-control investigation of hypoxic-ischemic encephalopathy of the newborn (HIEN) with reference to the 677C > T polymorphism as a genetic risk for this condition. The prevalence of the 677C > T allele was studied in 11 children with HIEN, their respective mothers, and 85 healthy individuals. Plasma homocysteine levels after fasting and methionine loading were determined in both mothers and controls. Ten of 11 patients were evaluated using magnetic resonance (MR) imaging, and all showed multicystic encephalomalacia and severe brain vasculopathy. Seven mothers were homozygous and four heterozygous for the 677C > T allele. Five of the children were homozygous and six heterozygous for this polymorphism. The variant allele frequency was higher in the group of mothers with affected children than in the controls and was associated with an increase in plasma homocysteine after methionine loading, in the group of mothers than in controls. The 677C > T mutation in mothers, either in a homozygous or heterozygous state, together with poor nutritional status (probable folate deficiency) may represent a risk factor for irreversible HIEN in the offspring.     

Meta analysis of the association between MTHFR C677T polymorphism and the risk of congenital heart defects

Methylenetetrahydrofolate reductase (MTHFR) polymorphism C667T has been associated with congenital malformation; this common missense mutation in the MTHFR gene may reduce enzymatic action, and may be involved in the etiology of congenital heart defects (CHD). The aim of this study was to investigate the relationship of the MTHFR C677T polymorphism with the risk of CHD in children with CHD and their parents by meta-analysis. Studies were identified by searching electronic literature for papers before 2011, focusing on MTHFR C667T and the risk of CHD. All data were analyzed using the fixed effects model in Cochrane Review Manager 5.1.1. Twenty eligible case-control and family-based studies were included. Overall analysis yielded pooled odds ratios (OR) of 1.55 (95%CI 1.25-1.93), 1.84 (95%CI 1.23-2.74) and 1.20 (95%CI 0.94-1.54) for fetal, paternal and maternal MTHFR TT genotypes in case-control studies, respectively, but yielded a summarized OR of 0.9 (95%CI 0.97-1.12) in family-based studies. Our results suggested that the fetal and paternal MTHFR C667T gene may be associated with an increased occurrence of CHD. Further larger studies should be performed to investigate the interaction between maternal genetic polymorphism, folic acid intake and hyperhomocysteinemia, and the development of CHD.     

MTHFR基因C677T多态性与神经管缺损的相关性研究

目的探讨5,10-甲基四氢叶酸还原酶（5,10-methylenetetrahydrofolate reductase,MTHFR）基因C677T突变与神经管缺损（neuraltube defectes,NTD）发病的相关性。方法应用PCR—RFLP法,对67名正常儿童和48例NTD患儿（NTD组）（其中无脑儿16例,脊柱裂32例）进行MTHFR基因C677T突变分析。结果NTD组胎儿MTHFR基因TT基因型频率（68．7％）和T等位基因频率（0．820）均显著高正常对照组儿童（31．3％和0．54）（x^2=15．71,P〈0．01和x^2=17．18,P〈0．01）。与MTHFR基因CC基因型相比,携带TT基因型的胎儿发生NTD的相对风险增加6．28倍（95％CI：2．01～19．62）。结论MTHFR基因C677T多态性与潍坊地区人胎儿NTD发病有关联。     

Single nucleotide polymorphism of NKX2-5 gene with sporadic congenital heart disease in Chinese Bai population

Background: Congenital heart disease (CHD) is the most common birth abnormality, especially for sporadic CHD. However, the etiology of sporadic CHD is largely unknown. NKX2-5, the earliest sign of cardiac progenitor cell differentiation, plays a key role in cardiac morphogenesis, and the mutation of this gene can cause sporadic CHD. Purpose: To investigate the association of genetic variations of NKX2-5 with sporadic CHD in Chinese Bai people. Methods: The whole 2 coding exons and flanking intron sequences of NKX2-5 gene were screened using DNA sequencing in 70 Chinese Bai patients with sporadic CHD and 136 healthy controls. Results: A novel heterozygous DNA sequence variant (DSV), 1433A>G, was identified in one tetralogy of Fallot (TOF) patient and one persistent left superior vena cava (PLSVC) patient, but none in controls. The frequency of single nucleotide polymorphism (SNP) rs2277923 in CHD group was significantly higher than that in control group. The allele and genotype were associated with the occurrence of CHD. Conclusion: The novel DSV (1433A>G) may be relevant with TOF and PLSVC, and the SNP rs2277923 of NKX2-5 gene contributes to the risk of sporadic CHD in Chinese Bai people.     

北京市10年围产儿先天性心脏病资料分析

目的分析北京市10年围产儿先天性心脏病发病情况，了解北京地区围产儿先天性心脏病发生情况。方法运用描述性统计学方法回顾性分析10年北京市出生缺陷监测资料。结果北京市围产儿先天性心脏病发病率呈现上升趋势；先天性心脏病合并其他畸形占先天性心脏病的9．60％，其中合并染色体畸形占第一位；单纯先天性心脏病发病类型前三位为室间隔缺损、动脉导管未闭、房间隔缺损。结论出生缺陷监测水平和诊断水平的提高是先天性心脏病发病率升高的主要原因；应该延长出生缺陷的监测时限；应该进一步加强专业技术培训，减少先天性心脏病的漏报。