洛阳地区不明原因复发性流产女性MTHFR基因C677T位点多态性分析

目的通过研究洛阳地区不明原因复发性流产女性患者亚甲基四氢叶酸还原酶(MTHFR)基因C677T位点多态性分布情况,探索其与不明原因复发性流产(URSA)的关系。方法采用荧光定量PCR方法对109例URSA女性患者和487例健康经产妇MTHFR基因C677T位点进行检测,对比两组女性的等位基因分布频率,分析其多态性与URSA的关系。结果 URSA组MTHFR基因C677T位点T/T型分布频率明显高于对照组,差异具有统计学意义(P0.05);T/T型女性发生URSA的危险性增加(OR=1.942,95%CI:1.012～3.726)。结论洛阳地区女性不明原因复发性流产与MTHFR基因C677T位点多态性相关。     

清远地区MTHFR基因多态性与原因不明复发性流产的相关性研究

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T位点单核苷酸多态性与原因不明复发性流产(URSA)的发生之间的相关性。方法采用前瞻性病例对照研究,选取清远地区71例URSA患者与76例两次正常生育妇女作为对照,采用实时定量PCR分析技术检测MTHFR基因C677T位点单核苷酸多态性情况,并用χ~2检验分析URSA组与对照之间的C677T位点基因型的差异。结果 URSA组MTHFR(C677T)基因纯合突变型TT及等位基因T的频率均高于正常对照组。结论清远地区不明原因复发性流产的发生与MTHFR基因C677T位点纯合突变型TT存在相关性。     

叶酸代谢酶MTHFR基因多态性与不明原因复发性流产的相关性研究

目的初步探讨亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C位点单核苷酸多态性与苏南地区不明原因的复发性流产(URSA)发生的相关性。方法采用病例对照研究的方法,对170例苏南地区不明原因复发性流产者(病例组)和170例正常妇女(对照组),利用PCR荧光探针技术检测MTHFR基因C677T、A1298C位点的单核苷酸多态性。结果病例组MTHFRC677T位点的TT基因型的发生频率显著高于对照组,T等位基因频率同样高于对照组,差异均有统计学意义(P0.05),而病例组MTHFR基因A1298C位点的CC基因型频率和C等位基因频率与对照组的相比,差异均无统计学意义(P0.05)。结论苏南地区MTHFR基因C677T位点多态性与育龄妇女发生不明原因复发性流产有一定的相关性。     

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...     

血浆Hcy水平及MTHFR和MTRR基因多态性与复发性流产的相关性研究

目的探讨血清同型半胱氨酸(Hcy)水平及亚甲基四氢叶酸还原酶(MTHFR)、甲硫氨酸合成酶还原酶(MTRR)基因多态性与不明原因复发性流产的相关性。方法以84例复发性自然流产的患者作为病例组,60例已有1次正常生育史,且既往无不良孕产史的妇女作为对照组,应用荧光定量PCR技术检测MTHFR基因C677T、A1298C和MTRR A66G位点的多态性,同时应用比色法检测血清Hcy水平。比较病例组和对照组间各种基因型和血清Hcy水平的差异。结果病例组血清Hcy水平明显高于对照组;高Hcy是先兆流产的危险因素(OR=2.132,P=0.021);MTHFR C677位点TT基因型携带者血清Hcy水平明显高于其他基因型;A1298位点CC基因型携带者血清Hcy水平明显高于AA野生型;MTRR A66位点GG基因型携带者血清Hcy水平明显高于其他基因型,差异均有统计学意义(P0.05)。结论 Hcy升高是导致复发性流产的重要危险因素;MTHFR基因C677T、A1298C和MTRR A66G位点的多态性改变均可致血清Hcy水平升高,与复发性流产的发生有一定的相关性。     

血清同型半胱氨酸水平、亚甲基四氢叶酸还原酶基因多态性与糖尿病视网膜病变的相关性研究

目的探讨血清同型半胱氨酸（Hcy）水平、亚甲基四氢叶酸还原酶（MTHFR）基因的分布情况与糖尿病视网膜病变（DR）的关系。方法应用聚合酶链反应和限制性片断长度多态性（PCR-RELP）方法检测47例健康对照组和50例糖尿病视网膜病变患者MTHFR基因的677碱基多态性突变C—T情况，同时测定其血清Hcy水平和叶酸水平，进行对照分析。结果糖尿病视网膜病变患者MTHFR基因突变型C677T基因的频率明显高于对照组。差异有显著性（P〈0．05），且Hcy水平明显增高。在叶酸浓度≤6．92nmol／L时。DR组1Tr型发生频率及T等位基因频率明显高于对照组（P〈0．05）；但当叶酸浓度〉6．92nmol／L时。DR组TT型发生频率及T等位基因频率与对照组无差异（P〉0．05）。结论MTHFR基因C677T位碱基突变导致血浆Hcy水平升高是糖尿病视网膜病变发病的重要危险因素。但受叶酸浓度的影响。     

同型半胱氨酸和MTHFR基因多态性与Alzheimer病的关系

目的探讨同型半胱氨酸(Hcy)和5,10 亚甲基四氢叶酸还原酶(MTHFR)基因多态性与Alzheimer病的关系.方法运用多聚酶链反应限制性内切酶片段长度多态性技术(PCR RFLP)和荧光偏振法(FPIA)检测66例阿尔茨海默病及143例正常人MTHFR基因多态性和血浆总Hcy水平.结果 (1)AD病人甲基四氢叶酸还原酶基因中,基因型C/T占56.06%,明显高于对照组的34.97%(P<0.01,RR=0.355),C/C占39.39%,明显低于对照组的62.94%(P<0.01),T/T占4.25%,与对照组2.09%无明显差异(P>0.05). AD病人中甲基四氢叶酸还原酶基因等位基因C的频率为67.43%、相对危险率(RR)为0.594,T的频率为32.57%、与对照组的C为80.42%、T为19.58%有显著性差异(P≤0.05).(2)AD病例组与对照组血浆Hcy分别为14.72±6.2μmol/L和10.9±2.4μmol/L,两者差异有显著差异(P<0.05).AD患者血浆总Hcy水平显著高于正常组.结论 MTHFR基因突变及高同型半胱氨酸血症与Alzheimer病发生有一定关系.     

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。     

MTHFR基因多态性与血浆同型半胱氨酸在妊娠期高血压疾病的相关性研究

目的 探讨四氢叶酸还原酶（MTHFR）C677T基因多态性及血浆同型半胱氨酸（Hcy）在妊娠期高血压疾病（HDP）发病机制中的作用。方法 用过枉法提取基因型DNA，并行聚合酶链反应物-直接测序法检测和分析MTHFR基因中C677T的分型，用微粒酶免疫发光法测量血浆同型半胱氨酸水平。结果 ①HDP组与对照组C677／T677比较差异有统计学意义（P〈0．05），HDP组T677等位基因频率（0．488）显著高于对照组（0．325），两组比较差异有统计学意义（P〈0．01）。②轻度子痫前期组、重度子痫前期组的血浆Hcy水平均高于对照组，分别比较，差异均有统计学差异（P〈0．001）。结论 ①妊娠期高血压疾病患者的MTHFR C677T基因多态性可能是妊娠期高血压疾病发生的诱因之一，T667等位基因可能是妊娠高血压疾病的易感基因。②血浆Hcy水平升高可能是子痫前期发病的危险因素。     

育龄女性机体叶酸浓度及MTHFR基因多态性与胎儿出生缺陷的相关性分析

目的研究育龄女性机体叶酸浓度及亚甲基四氢叶酸还原酶(MTHFR)基因多态性与胎儿出生缺陷的相关性分析。方法选取我院2016年01月～2020年01月胎儿出生缺陷育龄女性87例作为观察组,另选我院同期收治的无胎儿出生缺陷育龄女性90例作为对照组,对两组孕妇孕期体内叶酸浓度,MTHFR基因多态性进行观察记录,并对叶酸浓度、MTHFR与胎儿出生后缺陷的相关性进行分析。结果观察组MTHFR C677T位点基因多态性分布中,C/C基因型频率显著低于对照组,C/T、TT显著高于对照组,等位基因频率中C显著低于对照组,T显著高于对照组,差异具有统计学意义(P0.05);MTHFR A1298C位点基因多态性分布,A/A基因型频率显著低于对照组,A/C、C/C显著高于对照组,等位基因频率A显著低于对照组,C显著高于对照组,差异具有统计学意义(P0.05)。观察组叶酸浓度水平显著低于对照组,观察组不同基因多态性中各频型叶酸浓度显著低于对照组,差异具有统计学意义(P0.05)。对观察组孕妇进行ROC曲线分析结果显示敏感度90.8%,特异度90.0%。经过多因素Logistic回归分析中显示,T/T、C/T、A/C、C/C基因型为导致出生缺陷的独立危险因素。结论胎儿缺陷孕妇其体内叶酸浓度与无胎儿缺陷孕妇存在显著差异,其MTHFR基因多态性也存在显著差异,叶酸浓度对预测胎儿缺陷具有一定临床价值。     

叶酸代谢酶基因多态性与反复自然性流产易感性的研究

目的探讨叶酸代谢相关酶基因多态性在不明原因反复自然流产遗传易感性中的作用地位。方法运用聚合酶链反应-限制性片段长度多态性技术（PCR—RFLP）检测蛋氨酸合成酶还原酶（MTRR）A66G,蛋氨酸合成酶（MS）A2756G,N5,10-亚甲基四氢叶酸还原酶（MTHFR）C677T,胱硫醚β-合成酶（CBβS）844ins68基因多态性。结果不明原因反复自然流产患者MTHFR的T等位基因突变频率较正常对照组明显升高。而MS、MTRR和CBβS突变频率在病例组与对照组之间无显著差异。结论MTHFR C677T基因突变多态性可作为不明原因反复自然流产预后的检测指标。     

PAI-1基因和MTHFR基因多态性与复发性早期自然流产的关系

目的探讨纤溶酶原激活剂抑制物1(plasminogenactivatorinhibitor1,PAI1)基因和亚甲基四氢叶酸还原酶(methylenetetrahydrofolatereductase,MTHFR)基因多态性与复发性早期自然流产(recurrentearlyspontaneousabortion,RESA)的相关性。方法选取127例RESA非妊娠患者和117名健康非妊娠妇女,应用聚合酶链反应限制性片段长度多态性分析技术检测PAI1基因-675位4G/5G多态性和MTHFR基因C677T位点多态性。结果(1)患者组PAI1基因4G/4G基因型频率(45.7%)和4G等位基因频率(66.1%)显著高于对照组(17.1%和46.6%)(P<0.01),与5G/5G基因型比较,4G/4G型患者发生RESA的相对风险率的比数比(oddsratio,OR)为4.8,95%的可信区间(confidenceinterval,CI):2.23～10.35;(2)MTHFR基因T/T基因型和T等位基因频率患者组(43.3%和66.5%)显著高于正常对照组(21.4%和52.6%)(P<0.01),与C/C基因型比较,T/T型患者发生RESA的相对风险率为OR=3.2,95%CI:1.40～7.30;(3)RESA患者若同时兼有4G/4G和T/T基因型时,发生自然流产的相对风险率明显增加,OR=6.20,95%CI:2.62～14.67。结论PAI1基因4G/5G多态性和MTHFR基因C677T位点多态性与不明原因RESA密切相关,易感基因型4G/4G型和T/T型对RESA的发生具有协同作用。     

Influence of combined methionine synthase (MTR 2756A > G) and methylenetetrahydrofolate reductase (MTHFR 677C > T) polymorphisms to plasma homocysteine levels in Korean patients with ischemic stroke

PURPOSE: Methionine synthase (MTR) and 5,10-methylenetetrahydrofolate reductase (MTHFR) are the main regulatory enzymes for homocysteine metabolism. The present case- control study was conducted to determine whether there is an association between the MTR 2756A > G or MTHFR 677C > T polymorphism and plasma homocysteine concentration in Korean subjects with ischemic stroke. MATERIALS AND METHODS: DNA samples of 237 patients who had an ischemic stroke and 223 age and sex-matched controls were studied. MTR 2756A > G and MTHFR 677C > T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Frequencies of mutant alleles for MTR and MTHFR polymorphisms were not significantly different between the controls and cases. The patient group, however, had significantly higher homocysteine concentrations of the MTR 2756AA and MTHFR 677TT genotypes than the control group (p=0.04 for MTR, p=0.01 for MTHFR). The combined MTR 2756AA and MTHFR 677TT genotype (p= 0.04) and the homocysteine concentrations of the patient group were also higher than those of the controls. In addition, the genotype distribution was significant in the MTHFR 677TT genotype (p=0.008) and combined MTR 2756AA and MTHFR 677TT genotype (p=0.03), which divided the groups into the top 20% and bottom 20% based on their homocysteine levels. CONCLUSION: The results of the present study demonstrate that the MTR 2756A > G and MTHFR 677C > T polymorphisms interact with elevated total homocysteine (tHcy) levels, leading to an increased risk of ischemic stroke.     

MTHFR C677T多态性与脓毒血症的关系

目的 探讨MTHFR C677T基因多态性（SNP）与脓毒血症的关系。方法 选择2014年1月~2018年6月我院住院的脓毒血症患者98例,采用梯度PCR及DNA测序技术,检测MTHFR C677T基因型,比较不同T淋巴细胞凋亡比例脓毒血症患者MTHFR C677T基因型分布情况及MTHFR C677T多态性与脓毒血症的关系。结果 MTHFR C677各位点基因型在T淋巴细胞中的凋亡比例方面比较,差异均无统计学意义（P＞0.05）;APACHEⅡ＜4分,SOFA＜2分的CT比例高于CC与TT基因型,降钙素原减少比例TT低于CC基因型与CT基因型,差异均有统计学意义（P＜0.05）,28 天死亡人数比例TT低于CC基因型与CT基因型,差异均有统计学意义（P＜0.05）。结论 MTHFR C677T与脓毒血症患者预后有关,可根据MTHFR C677T的基因多态性预测脓毒血症的预后。     

亚甲基四氢叶酸还原酶基因多态性与青海汉族妊娠期高血压疾病的相关性

目的 探讨亚甲基四氢叶酸还原酶（MTHFR）基因-677C/T（rs1801133）多态性与青海汉族妇女妊娠期高血压疾病（HDP）的相关性。 方法 选择青海省HDP患者 139 例（HDP组）,正常妊娠孕妇 145 例（对照组）,应用限制性内切酶片段长度多态性聚合酶链反应（PCR-RFLP）方法,检测HDP组和对照组MTHFR-677C/T多态性分型并测序验证。 结果 HDP组和对照组MTHFR基因CC、CT、TT基因型频率分别为54.68%、35.25%、10.07% 和69.66%、22.06%、8.28%,CC基因型频率HDP组54.68%低于对照组69.66%（P<0.05）,CT基因型频率HDP组35.25%高于对照组22.06%（P<0.05）,而TT基因型频率HDP组和对照组之间差异无统计学意义（P>0.05）;HDP组和对照组MTHFR-677C/T多态性C和T等位基因频率分布有差异（P<0.05）,HDP组T等位基因频率高于对照组（χ²=5.568,P<0.05）。 结论 MTHFR基因-677C/T多态性与青海汉族HDP相关,MTHFR基因-677C/T多态性中T等位基因可能是HDP的易感基因,CT基因型为HDP的易感基因型。     

Gene-gene interaction between fetal MTHFR 677C>T and transcobalamin 776C>G polymorphisms in human spontaneous abortion

BACKGROUND: Genetic polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and transcobalamin (TC) genes influence homocysteine metabolism which in turn may influence the risk of spontaneous abortion. It was hypothesized that there may be a significant interaction between MTHFR and TC genotypes which affects the pathogenesis of spontaneous abortion. METHODS AND RESULTS: A total of 76 fetal tissue samples from spontaneous abortions between weeks 6 and 20 of pregnancy, and 114 control samples from healthy blood donors were genotyped for the MTHFR 677C>T and 776C>G polymorphisms. Subjects with combined MTHFR 677TT/TC 776GG and combined MTHFR 677TT/TC 776CG genotypes gave an odds ratio for spontaneous abortion of 3.8 (95% confidence interval 1.4-9.9, P = 0.005). CONCLUSIONS: Embryos that have combined MTHFR 677TT and TC 776CG or 776GG genotypes; genotypes that individually are associated with impaired homocysteine metabolism in adults, are at increased risk for spontaneous abortion compared with embryos that have only one of these genotypes.     

Methylenetetrahydrofolate reductase polymorphism (c677t) in muslim population of eastern uttar pradesh, India

Objective : The aim of the present study was to investigate the distribution of methylenetetrahydrofolate reductase (C677T) polymorphism in the Muslim population of eastern Uttar Pradesh. Materials and Methods: Total 56 subjects were analysed for MTHFR C677T polymorphism. C677T mutation analysis was done according to the PCR-RFLP (Polymerase chain reaction-Restriction fragment length polymorphism) method. Results : The frequencies of three genotypes CC, CT, and TT were 0.857, 0.125, and 0.07, respectively, and the frequency of mutated T allele was found to be 0.080. Conclusion : Genotypes and allele frequencies revealed the low prevalence of MTHFR C677T polymorphism in Indian Muslims. C677T mutation has been suggested to be positively associated with the risk of several congenital and multifactorial disorders. The low frequency of T/T genotype in the Muslim population may be due to malnutrition in pregnant women, because of insufficient intake of folate is considered to be a survival disadvantage for foetuses with T/T genotype.     

eNOS基因和MTHFR基因多态性与子痫前期发病关系的研究

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突变与子痫前期的关系。方法应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,对53例子痫前期患者(子痫前期组)和49例正常妊娠妇女(对照组)的eNOS基因G894T突变和MTHFR基因C677T突变进行检测。结果子痫前期组eNOS基因Glu/Glu、Glu/Asp、Asp/Asp基因型频率分别为71.7%、28.3%、0.0%;MTH-FR基因CC、CT、TT基因型频率分别为22.7%、39.6%、37.7%。对照组eNOS基因Glu/Glu、Glu/Asp、Asp/Asp基因型频率分别为83.7%、16.3%、0.0%;MTHFR基因CC、CT、TT基因型频率分别为20.4%、61.2%、18.4%。子痫前期患者TT基因型频率(37.7%)显著高于对照组(18.4%)(P<0.05),而CT基因型频率子痫前期组(39.6%)显著低于对照组(61.2%)(P<0.05),而eNOS基因型和等位基因频率两组比较差异均无显著性(P>0.05)。携带TT基因型个体发生子痫前期的风险增加2.69。结论eNOS基因G894T突变与子痫前期发病无关;MTHFR基因TT基因型能增加子痫前期的患病风险;eNOS基因和MTHFR基因在子痫前期发病中无协同作用。     

Folate gene polymorphisms and the risk of Down syndrome pregnancies in young Italian women

Maternal impairments in folate metabolism and elevated homocysteinemia are known risk factors for having a child with Down syndrome (DS) at a young age. The 80G>A polymorphism of the reduced folate carrier gene (RFC-1) has been recently demonstrated to affect plasma folate and homocysteine levels, alone or in combination with the 677C>T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene. We performed the present study on 80 Italian mothers of DS individuals, aged less than 35 at conception, and 111 Italian control mothers, to study the role of the RFC-1 80G>A, MTHFR 677C>T, and MTHFR 1298A>C genotypes to the risk of a DS offspring at a young maternal age. When polymorphisms were considered alone, both allele and genotype frequencies did not significantly differ between DS mothers and control mothers. However, the combined MTHFR677TT/RFC-1 80GG genotype was borderline associated with an increased risk (OR 6 (CI 95%: 1.0-35.9), P = 0.05), and to be MTHF1298AA/RFC-1 80(GA or AA) was inversely associated with the risk (OR 0.36 (CI 95%: 0.14-0.96), P = 0.04). Present results seem to indicate that none of the RFC-1 80G>A, MTHFR 677C>T, and MTHFR 1298A>C polymorphisms is an independent risk factor for a DS offspring at a young maternal age; however, a role for the combined MTHFR/RFC-1 genotypes in the risk of DS pregnancies among young Italian women cannot be excluded.     

Polymorphisms of methylenetetrahydrofolate reductase gene among women of childbearing age from Shiyan areaCSCD

Objective: To assess the association of methylenetetrahydrofolate reductase (MTHFR) gene 677C>T polymorphism with blood homocysteine (Hey) level among women of childbearing age from Shiyan area. Methods: PCR - chip hybridization was used to determine the genotype of MTHFR 6770T, and a biochemical assay was used to determine the total Hey level among 428 healthy women of childbearing age. Association of MTHFR 677>T with total Hey level was assessed. Results: Heterozygous CT mutation was most common form for the MTHFR 677>T polymorphisms and amounted for 49. 77% among the group, while the CC wild type and homozygous TT mutation respectively accounted for 30. 61% and 19. 63%. These gave a frequency of 44. 51% for the 677T allele. The dominant genotype among different age groups were the CT type. Of note, the proportion of MTHFR 677CC is higher in women above 30 years of age. The distribution of MTHFR 677>T genotypes has differed significantly among different age groups (P<0. 05). Compared with those with wild type alleles, carriers of MTHFR mutations had a higher plasma Hey level. The genotypic frequencies of MTHFR C677T in Shiyan region differed significantly from those of Sichuan, Hebei, Henan and Shandong (P < 0. 05) but were similar to those of Jiangsu, Guangdong, Ningxia and Xinjiang. Conclusion: The distribution of MTHFR C677T polymorphism among women of childbearing age in Shiyan area is influenced by age and is geographically specific and associated with plasma Hey level. Nearly 50% of women have carried the high risk alleles, for whom folic acid supplementation is crucial for the reduction of birth defect rate. © 2018 MeDitorial Ltd. All rights reserved.