中国北方少数民族人群同型半胱氨酸代谢酶的遗传多态性

目的 了解我国北方地区３个少数民族人群中ＭＴＨＦＲ和ＣＢＳ基因的遗传多态性，获得ＭＴＨＦＲ Ｃ６７７Ｔ和Ａ１２９８以及ＣＢＳ Ｔ８３３Ｃ和Ｇ９１９Ａ位点的群体遗传学数据。方法 应用ＰＣＲ－ＲＦＬＰ，ＰＣＲ－ＡＲＭＳ技术分别调查了吉林延边朝鲜族、新疆乌鲁木齐维吾尔族和回族新生儿的基础型分布。结果 回族和朝鲜族ＭＴＨＦＲ６７７纯合突变频率为１６．７％和２０．９％，与中国北方人群的总体水平基本一致，而维     

5,10—亚甲基四氢叶酸还原酶多态性和神经管畸表的病例对照研究

目的 探讨北方乡村妇女亚甲基四氢叶酸还原酶（ＭＴＨＦＲ）基因多态性与神经管畸形的关系。方法 用聚合酶链反应－限制性片段的多态性（ＰＣＲ－ＲＦＬＰ）技术,检测２０例生育神经管畸形患儿（ＮＴＤｓ）的妇女及７６例农村和７３例城市正常出生儿母亲的ＭＴＨＦＲ基因多态性。结果ＭＴＨＦＲ基因第６７７位核苷酸呈多态性,可分为三种类型：Ｃ／Ｃ、Ｃ／Ｔ、Ｔ／Ｔ。病例组三种基因突变频率：Ｃ／Ｃ,５％;Ｃ／Ｔ,５０％;Ｔ     

同型半胱氨酸代谢异常与原发性高血压的病例对照研究

目的 探讨同型半胱氨酸代谢异常与原发性高血压的关系。方法 从上海市一个社区中随机选取１２７例３５～７５岁的原发性高血压病人和１７０例正常血压者。使用高效液相色谱结合电化学方法检测血清中同型半胱氨酸总浓度,使用放射免疫法同时测定血清中叶酸和Ｂ１２浓度。采用聚合酶链反应－限制性片段长度多态性分析亚甲基四氢叶酸还原酶（ＭＴＨＦＲ）基因多态性。结果 调整年龄和性别后,病例和对照组同型半胱氨酸水平分别为１０     

EB病毒转化的永生性人B淋巴母细胞中的MTHFR基因的表达

为检测用ＥＢ病毒转化建立的永生性人Ｂ淋巴细胞株中Ｎ＾５,Ｎ＾１０－亚甲基甲氢叶酸还原酶（ＭＴＨＦＲ）基因的表达及其ｃＤＮＡ序列,用ＥＢ病毒转化人外周血Ｂ淋巴细胞,建立永生性细胞株后,从培养细胞中提取总ＲＮＡ,用ＲＴ－ＰＣＲ法扩增ＭＴＨＦＲ基因ｃＤＮＡ的不同片段,进行ＰＡＧＥ电泳分析和ｃＤＮＡ序列测定。结果显示永生性人Ｂ淋巴母细胞中有ＭＴＨＦＲ基因表达,其ｃＤＮＡ序列与文献报道的人肝脏ＭＴＡＨＦＲ基     

血浆同型半胱氨酸与叶酸,维生素B12及还原酶的关系

目的 探讨叶酸、维生素Ｂ１２（ＶＢ１２）、血浆总同型半胱氨酸、５、１０－亚甲基四氢叶酸还原酶（ＭＴＨＦＲ）活性及其热敏感性基因型间的相互关系。方法 研究为３４例生育神经管畸形ＮＴＤＳ）儿的母亲及４２例生育正常儿的母亲,检测指标包括ｔＨｃｙ、红细胞叶酸、血清叶酸和ＶＢ１２、ＭＴＨＦＲ酶活性及热敏感性。ｔＨｃｙ、红细胞叶酸、血清叶酸在病例组与对照组间差异无统计学意义;ＮＴＤＳ患儿母亲ＶＢ１２显低于正     

随机引物聚合酶链反应对耐甲氧西林金黄色葡萄球菌基因分型的研究

目的建立耐甲氧西林金黄色葡萄球菌（ＭＲＳＡ）随机引物聚合酶链反应（ＡＰ－ＰＣＲ）基因分型的方法用于；临床流行病学调查。方法优化ＡＰ－ＰＣＲ方法并与抗生素敏感谱分型法比较，评价ＡＰ－ＦＣＲ基因分型法的可靠性与分辨力；并对４９株ＭＲＳＡ进行ＡＰ－ＲＣＲ基因分型。结果４９株医院感染的ＭＲＳＡ可分为１０个ＡＰ－ＰＣＲ谱型，主要谱型为 Ａ３型，分型率 １００％；其中 ４１株 ＭＲＳＡ为流行病学相关株。结论 ＡＰ－ＰＣＲ基因分型是一种经济、快捷、可靠的分型方法；是在分子水平上对微生物感染进行病原学、发病机理及流行病学研究较理想的工具。     

鸡胚微量中同型半胱氨酸,叶酸,HCY—2抗体水平和MTHFR基因型检测？…

为建立鸡胚胎尿绒膜一血采集方法和检测胚胎血中同型半胱氨酸（ＨＣＹ）、叶酸、ＨＣＹ－２抗体及亚甲基四氢叶酸还原酶（ＭＴＨＦＲ）基因型变化情况,采用ＨＰＬＣ法测血浆总ＨＣＹ,ＰＣＲ－ＲＦＬＰ法测纸血片ＭＴＨＦＲ,ＳＬＩＳＡ法测血清ＨＣＹ－２抗体和微生物法测纸血片血红蛋白叶酸盐。结果发现连续７ｄ给Ｄ．Ｌ－ＨＣＹ后,鸡胚血浆总ＨＣＹ浓度（１０６．９２μｍｏｌ／Ｌ）显著高于正常对照组（１４．１６μｍｏｌ／Ｌ     

血管紧张素原基因多态性与原发性高血压关系的研究

目的 探索血管紧张素原（ＡＧＴ）的Ｍ２３５Ｔ多态性与上海市嘉定区望新乡原发性高血压的关系。方法 以人群为基础进行高血压病例－对照研究,应用ＰＣＲ－ＲＦＬＰ技术,分析ＡＧＴ的Ｍ２３５Ｔ多态性。结果 望新乡高血压病例组中ＡＧＴ基因ＴＴ基因型频率显著高于对照组,分别为４２．８％和３３．０％。相对于ＭＭ基因型,暴露于ＴＴ基因型的ＯＲ值为３．６１。病例组中Ｔ等位基因的频率也显著高于对照组,分别为７３．８９％     

恙螨体内肾综合征出血热病毒基因的套式PCR检测

目的：检测恙螨体内微量肾综合征出血热病毒（ＨＦＲＳＶ）基因。方法：选择ＨＦＲＳＶ膜蛋白（ＭＰ）基因的保守区核苷酸序列合成两对引物，采用异硫氰酸胍一步抽提ＲＮＡ，建立了反转录聚合酶链反应（ＲＴ－ＰＣＲ）检测鼠体恙螨及游离恙螨体内ＨＦＲＳＶ－ＲＮＡ的方法，扩增产物经凝胶电泳及点印迹杂交证实具有特异性。结果：ＨＦＲＳＶ抗原阳性鼠体恙螨５０只组、１０只组、游离恙螨５０只组，经ＲＴ－ＰＣＲ检测为阳性；ＨＦＲＳＶ抗原阳性鼠体恙螨５只组，ＨＦＲＳＶ抗原阴性鼠体恙螨５０只、１０只和５只组，游离螨１０只和５只组均未见明显扩增带。进一步用ＮｅｓｔｅｄＲＴ－ＰＣＲ检测，在ＲＴ－ＰＣＲ未检测出ＨＦＲＳＶ－ＲＮＡ各组中均检测有ＨＦＲＳＶ－ＲＮＡ，最低检出为５只螨组。并用核酸分子杂交技术进一步证实了上述结果。结论：ＮｅｓｔｅｄＲＴ－ＰＣＲ具有高特异、高敏感的特点，可用于检测恙螨体内微量ＨＦＲＳＶ－ＲＮＡ，从分子生物学角度为恙螨作为ＨＦＲＳＶ的传播媒介提供了直接证据。     

重庆市7—12岁儿童肺通气功能正常值的探讨

为评价儿童生长发育过程中肺通气功能的状况，对重庆市区１６３５名７－１２岁正常男女儿童的肺通气功能进行测量，计算不同性别，年龄组ＦＶＣ，ＦＥＶ１，ＦＥＶ１％，ＰＥＦＲ，ＭＭＥＦ，Ｖ７５，Ｖ５０和Ｖ２５等８项指标的平均数，标准差和８项指标与身高，体重的相关关系，并建立有关指标的正常预测值的回归方程。     

亚甲基四氢叶酸还原酶基因单体型与焦炉作业工人染色体损伤易感性的关系

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与焦炉作业工人染色体损伤易感性的关系。方法选取140名焦炉工和66名医护人员作为研究对象,采用胞质分裂阻滞微核实验评价个体染色体损伤水平,测定尿中1-羟基芘浓度反映多环芳烃暴露内剂量,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析MTHFR基因两个单核苷酸多态性(SNP)位点(C677T、A1298C),利用PHASE2·1软件经Bayesian法计算单体型。校正年龄、性别和尿1-羟基芘水平,用协方差分析比较MTHFR不同基因型或单体型之间外周血淋巴细胞微核率的差异。结果研究对象中MTHFRC677T和A1298C两个变异等位基因频率分别为0·56和0·16,其分布均符合Hardy-Weinberg平衡。本研究中MTHFR基因这两个SNPs存在连锁不平衡关系(D’=0·99),研究对象中有四种单体型677T-1298A、677C-1298A、677C-1298C和677T-1298C,其频率分别为0·555、0·279、0·163和0·003。在焦炉工组,非677C-1298A/677C-1298A单体型对的微核率高于677C-1298A/677C-1298A,差异有显著性(1·00±0·67vs0·60±0·41,P=0·04),其中677T-1298A/677T-1298A单体型对微核率高于677C-1298A/677C-1298A,差异有显著性(1·08±0·71vs0·60±0·41,P=0·04)。在焦炉工组和对照组中,未发现上述两个SNPs与微核率之间显著关联。结论MTHFR基因单体型可能是影响焦炉工染色体损伤的遗传易感性因素之一。     

四川南充市健康体检者同型半胱氨酸代谢酶基因多态性分布及其水平关联

目的 研究南充市汉族人群同型半胱氨酸(Hcy)代谢关键酶基因多态性的分布及与Hcy水平的关联.方法以在南充市中心医院的汉族人群470人为研究对象,抽取受检者血样,收集研究对象一般临床资料,采用循环酶法测定血浆Hcy水平,提取基因组DNA后进行SNP基因多态性检测,分析Hcy代谢关键酶MTHFR C677T、MTHFR ...     

Methylenetetrahydrofolate reductase (MTHFR) variants and bladder cancer: a population-based case-control study

Functional variants in the methylenetetrahydrofolate reductase (MTHFR) gene, including the 677C>T and 1298A>C polymorphisms, have been associated with a moderately reduced risk of several cancers, including colorectal cancers. While recent studies have investigated the role of these polymorphisms on bladder cancer susceptibility, results have been mixed. To clarify the role of MTHFR polymorphisms on bladder cancer risk, we genotyped MTHFR 677C > T and MTHFR 1298A > C in a population-based study of bladder cancer of 352 patients and 551 controls from New Hampshire, USA. The allelic frequency was 35.6% for MTHFR 677C>T and 40.4% for MTHFR 1298A > C among controls. We found no evidence of a main gene effect for either polymorphism (adjusted OR for MTHFR 677C>T variants versus the reference genotype = 1.1; 95% CI, 0.8-1.4 and adjusted OR for MTHFR 1298A>C variants versus the reference genotype = 1.0; 95% CI, 0.7-1.4). Odds ratios did not appear to differ by smoking status or gender. We observed differences in the risk estimates for the MTHFR polymorphisms by arsenic exposure, but they were not statistically significant (P = 0.67 for MTHFR 677C > T and P = 0.12 for MTHFR 1298A>C). Thus, our findings do not support the presence of a main gene effect. The possibility that MTHFR polymorphism affects susceptibility to environmental exposures warrants further consideration.     

亚甲基四氢叶酸还原酶基因多态性与2型糖尿病肾病的关系

目的探讨亚甲基四氢叶酸还原酶（methylenete—trahydrofolate reductase,MTHFR）基因多态性与2型糖尿病肾病（diabetic nephropathy,DN）的关系,为筛选DN高危人群及DN的早期干预治疗提供理论依据。方法采用以医院为基础的成组病例对照研究方法,于2009年6月至2010年1月对72例并发DN的2型糖尿病患者（病例组）和127例未并发DN的2型糖尿病患者（对照组）进行间卷调查、体格检查和实验室检查。应用聚合酶链反应-限制性片断长度多态性（PCR—RFLP）技术进行MTHFR基因C677T多态性分析。结果病例组MTHFR基因TT基因型和T等位基因频率分别为30．6％和54．9％,均高于对照组（17．3％和42．1％）,差异有统计学意义（P〈0．05o单因素logistic回归分析结果显示,MTHFR基因C677T多态性与DN之间存在统计学关联,其OR（95％CI）为1．673（1．100～2．545）;携带MTHFRT等位基因的2型糖尿病患者发生DN的危险性是C等位基因携带者的1．670倍（95％CI：1．106～2．521）,经过高血压、糖尿病病程和糖尿病家族史调整后,二者间的统计学关联仍然存在。结论MTHFR基因C677T多态性与DN相关,T等位基因可增加2型糖尿病患者合并肾病的危险。     

High plasma homocysteine is associated with the risk of coronary artery disease independent of methylenetetrahydrofolate reductase 677C-->T genotypes

Hyperhomocysteinemia is an independent risk factor for coronary artery disease (CAD). The aim of this study was to investigate the relations between the methylenetetrafolate reductase (MTHFR) 677C-->T genotypes, B-vitamins (folate, vitamin B-12 and B-6), homocysteine and the risk of CAD. In this case-control study, patients who were identified by cardiac catheterization as having at least 50% stenosis of one major coronary artery were assigned to the case group (n=121). Healthy individuals with normal blood biochemical values were assigned to the control group (n=155). Healthy subjects were matched to case subjects for age. The concentrations of plasma homocysteine, serum folate, vitamin B-12, plasma pyridoxal 5'- phosphate (PLP) and MTHFR 677C-->T gene polymorphism were obtained. The T-allele carriers had significantly higher plasma homocysteine concentration compared to subjects with the 677CC genotype. The MTHFR 677C-->T genotypes were associated with plasma homocysteine after adjusting for various potential risk factors in the case and pooled groups. The MTHFR genotypes were found to have no associations with the risk of CAD. However, plasma homocysteine (>or= 12.5 micromol/L) (OR, 3.49; 95% CI, 1.23-9.88) had a significant association with increased risk of CAD even after additionally adjusted folate status. High plasma homocysteine concentration had a direct effect on the risk of CAD independent of MTHFR 677C-->T genotypes.     

Lack of association between the C677T single nucleotide polymorphism of the MTHFR gene and glaucoma in Iranian patients

Glaucoma is a major cause of blindness worldwide. A single nucleotide polymorphism of the MTHFR gene (C677T) has been associated with susceptibility to this disease, although this is controversial in the last decade. In this study, the possible association between the MTHFR C677T polymorphism and the risk of developing primary open angle (POAG) and pseudoexfoliation glaucoma (PEXG) was investigated. For this, a prospective study consisting of 73 POAG, 85 PEXG and 90 matched controls was undertaken in an Iranian population. Genomic DNA was extracted from whole blood. Genotyping of all individuals for the MTHFR C677T polymorphism was conducted using the PCR-RFLP technique. Our findings revealed no significant association between the MTHFR C677T polymorphism in POAG and PEXG compared with controls. Consistent with several other studies, our analysis suggests that the MTHFR C677T polymorphism is unlikely to be a factor contributing to the risk of developing specific forms of glaucoma.     

Folic acid supplementation for 3 wk reduces pulse pressure and large artery stiffness independent of MTHFR genotype

BACKGROUND: Folic acid reduces plasma homocysteine and may be an important therapy for preventing cardiovascular disease. A key mechanism may be the reduction of arterial stiffness. OBJECTIVE: The effect of folic acid supplementation on blood pressure and large artery stiffness was examined in relation to methylenetetrahydrofolate reductase (MTHFR) genotype. DESIGN: Forty-one asymptomatic men with normal or high-normal ambulatory blood pressure (systolic: >130 to <145 mm Hg; diastolic: >80 to <90 mm Hg) participated. The study had a randomized, placebo-controlled, double-blind, crossover design that incorporated 3-wk treatments with 5 mg folic acid/d or matching placebo; each treatment was separated by a 4-wk washout phase. RESULTS: Folic acid reduced brachial pulse pressure by 4.7 +/- 1.6 mm Hg (P < 0.05) without changing mean arterial pressure. Systemic arterial compliance increased by 0.15 +/- 0.03 mL/mm Hg (P < 0.05) after folic acid treatment but did not change after placebo treatment. These responses did not significantly correlate with either homocysteine or folate plasma concentrations. MTHFR genotype CC homozygotes (without the 677C-->T polymorphism) with normal blood pressure had a larger reduction in homocysteine concentrations in response to folic acid than did T allele carriers. Blood pressure and arterial stiffness responses were independent of MTHFR genotype. CONCLUSION: Folic acid is a safe and effective supplement that targets large artery stiffness and may prevent isolated systolic hypertension.     

泸州汉族人群MTHFR基因多态性分布及育龄妇女该基因多态性与复发性流产相关性的研究

目的了解泸州市亚甲基四氢叶酸还原酶(MTHFR)基因多态性分布情况以及该单核苷酸多态性与复发性流产的相关性。方法选取2016-2018年在西南医科大学附属医院进行MTHFR基因检测的泸州汉族人群691例为研究对象,利用PCR-微阵列基因芯片法检测其C677T单核苷酸多态性,统计得出3种基因型的频率以及等位基因频率,并与全国其他地区已报道的多态性分布特征进行比较。结果泸州汉族人群CC、CT与TT基因型频率分别为39.2%、46.7%、14.0%,T等位基因频率为37.4%。其中女性T等位基因频率为38.1%,基因分布与纬度相近地区(N25°~31°)差异无统计学意义(P>0.05),与南方的海南、惠州及北方的西安、银川、赤峰、烟台人群差异有统计学意义(P<0.05)。在泸州育龄妇女中,复发性流产与MTHFR C677T基因多态性暂未发现存在直接关联。结论泸州地区汉族人群的MTHFR基因分布具有西南地区的分布特征,T等位基因频率整体呈现出随着纬度升高而升高的趋势。