内皮型一氧化氮合酶和N5，N10-亚甲基四氢叶酸还原酶基因多态性与苏皖地区汉族人群早发冠心病易感性的相关关系

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突变与苏皖地区汉族人群早发冠心病(PCAD)发病的关系.方法 采用病例对照研究的方法,应用聚合酶链反应-限制性片长多态性(PCR-RFLP)技术,分别检测131例PCAD患者(PCAD组)和131例年龄、性别相匹配的无冠心病者(对照组)的eNOS和MTHFR基因的单核苷酸多态性,判定其基因型并统计各基因型及等位基因的频率.结果 eNOS基因G894T多态性在PCAD组和对照组中的基因型分布(x2=2.072,P=0.355)和T等位基因频率(x2=0.727,P=0.394)差异均无统计学意义.MTHFR基因C677T基因型在PCAD组CT和TT型分布均高于对照组(x2 =14.290,P=0.001),T等位基因频率亦高于对照组(x2=16.339,P =0.000),差异有显著性(P＜0.05).Logistic回归分析显示,携带MTHFR基因C677TTT基因型是PCAD发病的独立危险因素.结论 eNOS基因G894T多态性可能与苏皖地区汉族人群PCAD发病无关;MTHFR基因677C/T多态性的TT基因型可能增加苏皖地区汉族人群PCAD的患病风险,T等位基因可能是PCAD的遗传易感基因.     

Combined Hyperlipidemia In A Single Subject With Tetraplegia: Ineffective Risk Reduction After Atorvastatin Monotherapy

Abstract

Background/Objective: Effects of atorvastatin (Lipitor) drug monotherapy (1 0 mg daily) on fasting blood Iipid profiles and cardiovascular disease (CVD) risks were examined for a single subject with C5-C6 tetraplegia. Routine fasting Iipid profiles were analyzed by standard biochemistry techniques for total cholesterol (TC) , triglycerides (TG) , low-density lipoprotein-cholesterol (LDL-C) , and high-density lipoprotein-cholesterol (HDL-C). Lipid profiles were analyzed on 3 occasions before drug therapy was initiated and 3 months after therapy commenced. The TC:HDL and LDL:HDL ratios were computed for all sampling times and used to assess pretreatment and post-treatment CVD risk.

Results: Fasting TC, TG, and LDL-C were all significantly reduced by therapy. The pretreatment HDL-C of 3 5 mg/ dl was lowered to 21 mg/ dl. As a result, the TC:HDL risk ratiowas only marginally reduced from 6 .6 to 6.4, whereas the LDL:HDL risk ratio remained unchanged by treatment.

Conclusions: In this man with tetraplegia, atorvastatin drug monotherapy rapidly lowered TC, TG, LDL-C, and HDL-C. However, the TC: HDL ratio, considered the best predictor of CVD risk, was unchanged.     

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.     

遗传性高铁血红蛋白血症分子诊断方法的研究

目的 探讨遗传性高铁血红蛋白血症的分子诊断方法。方法 采用RT-PCR和PCR产物直接测序法,对3例遗传性高铁血红蛋白血症患者细胞色素b5还原酶(b5R)cDNA编码区序列进行分析。通过基因组DNA的PCR-限制性酶切或PCR-序列测定,验证cDNA策略所检出的突变。结果 患者A的b5R cDNA在第527位碱基呈T/C杂合状态,第608位碱基呈G/A杂合状态;患者B的b5R cDNA在第170位碱基和第179位碱基均呈G/A杂合状态;患者C的b5R cDNA在第608位碱基呈G/A杂合状态,第791位碱基呈C/T杂合状态。基因组DNA策略与cDNA策略所得结果一致。结论 建立了遗传性高铁血红蛋白血症的分子诊断方法,并在3例患者中发现了3个以复合杂合子形式存在的、新的b5R基因突变。     

Methylenetetrahydrofolate reductase genotypes and predisposition to atherothrombotic disease; evidence that all three MTHFR C677T genotypes confer different levels of risk.

AIMS: Elevated plasma homocysteine is an independent risk factor for atherothrombotic disease. Individuals homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C allele exclusively accumulate 5methyltetrahydrofolate, the methyl donor for homocysteine remethylation, in their red blood cells; this contrasts with 677 TT homozygotes who also accumulate significant levels of non-methylated folate derivatives. Those with the MTHFR 677 TT, CT and CC genotypes may therefore differ qualitatively with respect to folate utilization and hence their capacity to remethylate homocysteine. This study was consequently designed to establish whether all three genotypes confer different levels of atherothrombotic risk. METHODS AND RESULTS: The risk of atherothrombotic disease conferred by the MTHFR 677 CT and 677 CC genotypes was assessed using a 'restricted' meta-analysis approach applied to subjects from the first ten studies reporting a significantly increased risk conferred by the 677 TT genotype. The defined risk of the TT genotype in each of these ten studies was judged by us to denote 'genetic vulnerability' in the populations from which subjects were drawn. After proportional adjustment for the greater number of case TT homozygotes, the CT and CC frequencies observed in cases were compared with expectations based on the frequencies of these genotypes in controls. The observed CT frequency among cases was higher than expected in eight of the ten studies. In the meta-analysis, which included 1857 cases and 2942 controls, 847 (45.6%) cases, instead of the 777 (41.8%) expected, had the MTHFR CT genotype (P=0.010). CONCLUSIONS: Our findings suggest that the three MTHFR C677T genotypes confer different levels of atherothrombotic risk in 'genetically vulnerable' populations: CT heterozygotes have an elevated risk over CC homozygotes. One explanation is that the CT genotype actively confers atherothrombotic risk. An alternative interpretation however, for which a biologically plausible mechanism is proposed, is that CC is a protective genotype.     

湖北松滋市汉族女性 MTHFR 和 MTRR 基因多态性分布

目的分析湖北省松滋地区女性亚甲基四氢叶酸还原酶（methylenetetrahydrofolatereductase,MTHFR）C677T、A1298C及甲硫氨酸合成酶还原酶（methioninesynthasereductase,MTRR）A66G基因多态性的分布特征。方法采用现况研究方法,以松滋市1077例女性为研究对象,提取其口腔黏膜上皮细胞的基因组DNA,通过荧光定量PCR方法检测MTHFR和MTRR基因多态性。统计分析本地区基因多态性的分布特征,并与已报道其他地区进行比较。结果松滋市女性的MTHFR677TT纯合突变基因型频率为15．41％,与四川省德阳市（13．80％）基本一致,差异无统计学意义（P〉0．05）;高于广东省惠州市（10．86％）、海南省琼海市（6．14％）,低于江苏省镇江市（21．84％）、河南省郑州市（34．5％）、山东省临沂市（35．03％）,均有极显著性差异（P〈0．01）。MTHFR1298CC纯合突变基因型的分布百分数为2．60％,与四川省德阳市（6．26％）基本一致,差异均无统计学意义（P〉0．05）;低于海南省琼海市（7．13％）、广东省惠州市（7．24％）,高于山东省临沂市（2．42％）,差异均有统计学意义（P〈0．01）。MTRR66GG纯合突变基因型频率为6．41％,与琼海市比较,差异有统计学意义（P〈0．01）。结论松滋市女性MTHFR和MTRR基因多态性分布具有地域特异性。     

MTHFR C677T基因多态性与浙江某地区汉族人群2型糖尿病患者急性脑梗死的相关性

目的 探讨亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与浙江某地区汉族人群2型糖尿病患者急性脑梗死的相关性.方法 选取2017年1月至2018年6月在台州市立医院住院患者、门诊及同期体检中心体检人群共396例,分为急性脑梗死合并2型糖尿病组(CIDM,125例)、单纯2型糖尿病组(DM,120例)和性别、年龄...     

惠州地区亚甲基四氢叶酸还原酶基因多态性特征分析

目的 调查惠州地区人群中亚甲基四氢叶酸还原酶(MTHFR)基因C677T位点多态性的分布特征,为个体化指导育龄妇女增补叶酸及有效地降低新生儿出生缺陷风险提供科学依据.方法 收集2017年6月至2019年12月在产前诊断中心门诊就诊的育龄妇女、妊娠期夫妇的外周血样本765例.采用PCR-荧光探针法检测MTHFR基因C67...     

MTHFR基因多态性和同型半胱氨酸在冠心病脑梗死和糖尿病中的分析

目的探讨冠心病、脑梗死、糖尿病患者亚甲基四氢叶酸还原酶（MTHFR）和血浆同型半胱氨酸（Hcy）的关系,对三个病种的MTHFR基因型进行分析。方法收集120例冠心病,214例脑梗死,112例糖尿病患者及98例健康体检者标本,采用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）技术检测MTHFRC677T基因,采用酶循环法检测血浆Hcy,比较四组MTHFRC677T基因多态性及血浆Hcy的差异。结果（1）MTHFR基因型在冠心病,脑梗死和糖尿病组与健康对照组间差异无统计学意义（P＝0．670）;（2）MTHFR基因频率在冠心病,脑梗死和糖尿病组与健康对照组间差异无统计学意义（P＝0．721）;（3）冠心病组和脑梗死组的MTHFR基因TT型患者的Hcy水平远远高于CC型和CT型患者（F＝6．212,P＝0．003;F＝44． 362,P＝0．000）。结论不同病种间MTHFR基因型和基因频率差异无统计学意义,但冠心病组和脑梗死组MTHFR基因TT型患者Hcy水平则远远高于CC型和CT型患者,差异有统计学意义。