亚甲基四氢叶酸还原酶G1793A基因多态性及高同型半胱氨酸血症与溃疡性结肠炎的相关性

目的 探讨亚甲基四氢叶酸还原酶(MTHFR)G1793A基因多态性、血浆同型半胱氨酸(Hey)、叶酸及维生素B12浓度与溃疡性结肠炎(UC)的关系.方法 在299例UC患者和764例正常对照者中,采用聚合酶链反应-限制性片段长度多态性(PCR-RELP)检测MTHFR G1793A基因多态性,循环酶法检测血浆Hey水平,微粒子免疫化学发光法检测血浆叶酸和维牛素B12浓度.结果 UC组MTHFR 1793(A)等位基因和(GA+AA)基因型频率明显比正常对照组增高(22.24%比14.20%,P<0.001;42.81%比26.97%,P<0.001);血浆Hey水平亦明显高于正常对照组[(20.67±6.42)mmol/L比(13.21±5.11)mmol/L,P<0.001],而叶酸和维生素B12浓度明显降低[(11.37±6.34)nmol/L比(14.89±7.21)nmol/L,P<0.001;(324.15±127.53)pmol/L比(421.54±128.45)pmol/L,P<0.001].另外,UC组中高同型半胱氨酸血症(Hhcy)(Hcy≥15 mmol/L)及叶酸缺乏(叶酸≤7 nmol/L)的发生率显著高于正常对照组(32.44%比25.78%,P=0.029;23.41%比17.01%,P=0.016).结论 MTHFR G1793A基因多态性、Hhcy、叶酸缺乏及低维生素B12水平与湖北汉族UC明显相关.Hcy代谢酶基因可能涉及UC的发病机制.     

亚甲基四氢叶酸还原酶基因多态性与缺血性卒中

近年来的研究表明,高同型半胱氨酸血症通过多种机制造成血管内皮损伤,破坏机体凝血和纤溶系统,影响脂质代谢,是卒中的独立危险因素.亚甲基四氢叶酸还原酶(MTHFR)是体内同型半胱氨酸代谢途径的关键酶,该酶含量不足或活性下降将直接导致同型半胱氨酸在体内的蓄积,从而引起高同型半胱氨酸血症.虽然许多研究发现MTHFR基因突变是该酶缺乏或活性下降的主要原因,但是MTHFR基因突变与缺血性脑血管病的相关关系目前颇有争议.文章就MTHFR基因多态性与缺血性卒中的关系进行综述.     

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。     

亚甲基四氢叶酸还原酶基因C677T、A1298C和G1793A多态性与血液透析患者血浆Hcy水平的关系

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T、A1298C和G1793A多态性与血液透析患者血浆同型半胱氨酸(Hcy)水平的关系。方法接受血液透析的慢性肾衰竭患者(疾病组)88例的外周血标本,采用直接测序法对MTHFR基因3个标签(C677T、A1298C和G1793A)单核苷酸多态性(SNPs)进行基因分型,选取同期92例健康体检者的外周血作对比(对照组),比较两组以上SNPs位点基因型和等位基因的分布差异,采用酶联免疫吸附法检测血浆Hcy水平并比较疾病组MTHFR基因SNPs位点各基因型的血浆Hcy水平,以比值比(OR)及其95%置信区间(CI)评价以上SNPs发生Hcy升高的风险情况。结果两组C677T和G1793A基因型和等位基因分布差异有统计学意义(P0.05),其中疾病组C677T TT基因型和T等位基因的比例及G1793A AA基因型和A等位基因的比例明显高于对照组(P0.05)。疾病组血浆Hcy水平为(38.25±4.67)μmol/L,显著高于对照组的(19.36±2.59)μmol/L(P0.05)。疾病组C677T TT型的血浆Hcy水平高于CC、CT型,CT型高于CC型,G1793A AA型的血浆Hcy水平高于GG、GA型,GA型高于GG型,差异均有统计学意义(均P0.05)。C677T TT基因型较CC型血浆Hcy水平升高的风险升高至3.429倍(P0.05),而GA、GA+AA型血浆Hcy水平升高的风险未改变(P0.05);以C等位基因为参照,携带T等位基因者Hcy水平升高的风险升高至2.050倍(P0.05)。A1298C、G1793A位点血浆Hcy水平升高的风险均未改变(P0.05)。结论MTHFR C677T和G1793A携带突变基因者的血浆Hcy水平升高,其中C677TT等位基因的血浆Hcy水平升高的风险升高,在预测血液透析患者血浆Hcy水平异常上有一定价值。     

亚甲基四氢叶酸还原酶基因多态性与糖尿病肾病研究进展

亚甲基四氢叶酸还原酶(MTHFR)催化5,10-亚甲基四氢叶酸转变为5-亚甲基四氢叶酸,后者作为同型半胱氨酸(Hcy)转变为甲硫氨酸的甲基供体.MTHFR基因突变使该酶存在缺陷,导致Hcy积聚,后者具有血管损伤作用,通过损伤血管内皮细胞、促进血小板聚集、细胞和间质增生及胶原合成等参与糖尿病肾病发展的病理过程.     

冠心病患者亚甲基四氢叶酸还原酶基因多态性87例研究

目的探讨N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性与冠心病的关系。方法对2003年11月至2005年8月贵阳医学院附属医院及贵州市第二人民医院住院的87例冠心病患者(冠心病组)及同期在门诊进行健康体检的73名健康人(对照组),采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测其MTHFRC677T基因多态性。结果对照组与冠心病组MTHFR677位T等位基因的分布频率分别是18.5%,36.1%,病例组MTHFR基因C677T的CT基因型及T等位基因频率显著高于对照组,差异有显著性(P<0.05)。结论MTHFRC677T基因多态性与冠心病密切相关。     

2型糖尿病肾病亚甲基四氢叶酸还原酶基因多态性研究

目的探讨亚甲基四氢叶酸还原酶(methylenetetrahydrofolate     

胃癌组织中叶酸水平与代谢酶亚甲基四氢叶酸还原酶基因多态性的关系研究

目的探讨人胃癌组织中叶酸水平与代谢酶亚甲基四氢叶酸还原酶(MTHFR)基因多态性的变化及其关系。方法收集38例晚期胃癌患者的癌区、癌旁和外周正常区域组织标本,以自动化学发光系统测定人胃癌组织叶酸含量,PCR-限制性内切酶片段长度多态性技术检测MTHFR基因677(C→T)和1298(A→C)两个常见多态,并以34例慢性浅表性胃炎(CSG)组织作为对照,分析叶酸、MTHFR基因多态性的变化及其关系。结果CSG对照组中叶酸含量[(5.48±2.15)ng/ml]明显高于胃癌组织[癌区(3.65±1.97)ng/ml,癌旁(4.01±2.11)ng/ml,外周正常组织(4.00±2.20)ng/ml],胃癌组织MTHFR基因的两个多态位点中,677CT基因型叶酸含量最高,而1298(A→C)多态则未见明显差异。677TT基因型与CC基因型相比有减少胃癌发生的趋势,但与其生物学行为关系不密切。677TT基因型高叶酸组与CC基因型低叶酸组相比发生胃癌的相对风险度为0.11(95%CI:0.01~1.02)。癌组织标本检测中未发现1298CC基因型。结论组织叶酸含量降低者发生胃癌风险明显增加。MTHFR基因多态性并不是胃癌的一个孤立危险因素,它和组织叶酸含量共同作用于胃癌发生。     

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.     

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer susceptibility

AIM: To identify the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and gastric cancer (GC) susceptibility.METHODS: Systematic searches were performed on the electronic databases PubMed, ISI, Web of knowledge, CNKI and Wanfang, as well as manual searching of the references of the identified articles. A total of 26 papers were included in this meta-analysis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95%CI were used to evaluate the associations between MTHFR polymorphisms and GC risk. The I² statistics were used to evaluate between-study heterogeneity. Sensitivity analysis was also performed.RESULTS: Increased risk was found for the MTHFR C677T polymorphism under four genetic models (TT + CT vs CC: OR = 1.23, P = 0.002; T vs C: OR = 1.15, P = 0.001; TT vs CC: OR = 1.37, P = 0.0005; TT vs CT + CC: OR = 1.17, P = 0.0008). Subgroup analysis by ethnicity suggested that C677T polymorphism conferred a risk of GC in eastern but not in western populations. Stratification by tumor site showed an association between the C677T polymorphism and gastric cardia cancer and non-cardia GC in the worldwide population and in eastern populations. Regardless of comparisons with controls or diffuse-type GC, a positive association was found for the C677T polymorphism and an increased risk of intestinal-type GC in the whole population and in western populations. With regard to the A1298C polymorphism, we found that genotype CC was significantly decreased and conferred protection against GC in eastern populations (CC vs AA: OR = 0.44, P = 0.03; CC vs AC + AA: OR = 0.46, P = 0.04).CONCLUSION: MTHFR C677T polymorphism is a risk factor for GC, and the A1298C polymorphism may be a protective factor against GC in eastern populations.     

亚甲基四氢叶酸还原酶基因C677T多态性与高尿酸血症相关

采用PCR-RFLP方法检测高尿酸血症患者和正常对照者亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性,结果显示,山东沿海地区汉族人MTHFR基因C677T多态性与高尿酸血症相关,T等位基因是其危险因素,但与单纯高尿酸血症是否发展为痛风无关。     

An updated meta-analysis of methylenetetrahydrofolate reductase gene 677C/T polymorphism with diabetic nephropathy and diabetic retinopathy

Studies investigating the association of methylenetetrahydrofolate reductase (MTHFR) gene 677C/T polymorphism with diabetic nephropathy and diabetic retinopathy have so far reported inconclusive results. We therefore aim to address this inconclusiveness by conducting a meta-analysis. Random-effects model was applied irrespective of between-study heterogeneity. Data and study quality were assessed in duplicate. A total of 7807 and 1599 subjects from 21 and 8 studies were analyzed for diabetic nephropathy and diabetic retinopathy, respectively. Carriers of 677TT genotype were 1.71 (95% confidence interval [95% CI]: 1.02-2.88; P = 0.042) and 2.89 (95% CI: 1.51-5.53; P = 0.001) times more likely to develop diabetic nephropathy separately relative to diabetic patients without nephropathy and nondiabetic controls. Likewise, this association was preserved for diabetic patients with retinopathy referring to those without (odds ratio [OR] = 1.86; 95% CI: 1.21-2.86; P = 0.004). Subgroup analyses showed that ethnicity was a possible confounder, especially in West Asians and Africans, and so were gender and duration of diabetes mellitus in diabetic nephropathy studies. Probability of publication bias was low across all comparisons as reflected by the funnel plot and corresponding test. Taken together, our results demonstrate that MTHFR gene 677TT genotype might confer a moderately augmented risk for diabetic nephropathy and diabetic retinopathy.     

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。     

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and male infertility risk: An updated meta-analysis

Background:18 previous meta-analyses have been published on the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with male infertility risk. However, results of the previous meta-analyses were still inconsistent. Moreover, their meta-analyses did not assess false-positive report probabilities except one study. Furthermore, many new studies have been published, and therefore an updated meta-analysis and re-analysis of systematic previous meta-analyses were performed to further explore these issues.Objectives:To determine the association between MTHFR C677T and A1298C polymorphisms and male infertility risk.Methods:Crude odds ratios and their 95% confidence intervals were used to assess the association between MTHFR C677T and A1298C polymorphisms and male infertility risk. We used the Bayesian false discovery probability (BFDP) to assess the credibility of statistically significant associations.Results:Fifty-nine studies were included concerning the MTHFR C677T and 28 studies were found on the MTHFR A1298C with male infertility risk. Overall, the MTHFR C677T was associated with increased male infertility risk in overall populations, Africans, East Asians, West Asians, South Asians, azoospermia, and Oligoasthenoteratozoospermia (OAT). In further sensitivity analysis and BFDP test, the positive results were only considered as “noteworthy” in the overall population (TT vs CC: BFDP = 0.294, CT + TT vs CC: BFDP = 0.300, T vs C: BFDP = 0.336), East Asians (TT vs CC: BFDP = 0.089, TT vs CT + CC: BFDP = 0.020, T vs C: BFDP < 0.001), West Asians (TT vs CC: BFDP = 0.584), hospital-based studies (TT vs CC: BFDP = 0.726, TT vs CT + CC: BFDP = 0.126), and OAT (TT vs CT + CC: BFDP = 0.494) for MTHFR C677T. In addition, a significantly increased male infertility risk was found in East Asians and population-based studies for MTHFR A1298C. However, we did not find that the positive results were considered as “noteworthy” in the overall and all subgroup analyses for MTHFR A1298C.Conclusions:In summary, this study indicates that the MTHFR C677T is associated with increased male infertility risk in East Asians, West Asians, and OAT. No significant association was observed on the MTHFR A1298C with male infertility risk.     

IL-10单核苷酸多态性与溃疡性结肠炎的相关性研究

目的探讨血清IL-10水平、IL-10启动子区3个位点(IL-10-1082/-819/-592)的单核苷酸多态性(SNPs)与溃疡性结肠炎之间的相关性。方法选择溃疡性结肠炎患者60例(溃疡性结肠炎组),轻度24例、中—重度36例,并设健康对照组。采用ELISA法检测血清中IL-10,采用PCR-RFLP检测IL-10启动子区SNPs。结果中—重度溃疡性结肠炎患者血清IL-10水平低于健康对照组(P<0.05)。溃疡性结肠炎组IL-10-592位点AA型及AC型-819位点TT型和TC型与健康对照组比较有统计学差异(P均<0.05);两组IL-10-592位点CC型及IL-10-819位点CC型比较差异有统计学意义(P均<0.05);-592位点和-819位点基因型高度连锁。两组IL-10-1082位点AA型及GG型比较有统计学意义(P均<0.05)。结论 IL-10启动子区SNPs影响IL-10表达。血清IL-10的表达水平及其启动子区的不同基因型可反映溃疡性结肠炎的发病敏感性或活动度。     

亚甲基四氢叶酸还原酶基因677C/T多态性与上海地区2型糖尿病合并大血管并发症的关系

目的 研究亚甲基四氢叶酸还原酶（MTHFR）基因677C／T多态性与糖尿病大血管并发症（脑梗死和冠心病）之间的关系。方法 在416例中国人受试者中：大血管病变患者（AS组，即脑梗死亚组和冠心病亚组总和）216例，其中脑梗死亚组（CI）111例，该亚组中伴及不伴糖尿病患者分别为50例及61例；冠心病亚组（CHD）105例，该亚组中伴及不伴糖尿病患者分别为48例及57例。糖尿病无大血管病变者（DM）100例，正常对照（C）100例。研究方法采用PCR／酶解鉴定基因变异及群体关联分析。结果 大血管病变组中MTHFR基因的677C／T的TT基因型和T等位基因频率显著增高。Logistic回归分析表明MTHFR基因参与大血管病变（AS）的致病过程。大血管病变各组内糖尿病和非糖尿病两亚组间相互比较基因型频率差异没有显著性。大血管病变不同亚组按有无糖尿病及性别分层后可见高密度脂蛋白胆固醇及舒张压水平随基因型不同而差异有显著性。结论 在中国人中，不论有无糖尿病，MTHFR基因均参与大血管病变（脑梗死或冠心病）的致病过程。     

细胞毒T淋巴细胞相关抗原4基因多态性与溃疡性结肠炎

目的炎症性肠病的发病与T细胞过度活化有关,细胞毒T淋巴细胞相关抗原4（CTLA-4）是重要的T细胞活化负性调节因子.本课题研究CTLA-4基因启动子区-1722位点（T/C）及-1661位点（A/G）多态性与中国汉族人群中溃疡性结肠炎（UC）的相关性.方法采用PCR-限制性片段长度多态性方法,对87例中国汉族UC患者和116例正常对照者进行CTLA-4基因-1722位点和-1661位点多态性检测.结果UC患者CTLA-4基因-1661位点A/G＋G/G基因型频率,-1661位点G等位基因频率显著高于正常对照组（34.5%比15.5%,P=0.002,OR=2.865,95%CI=1.467～5.596;19.0%比8.2%,P=0.002,OR=2.624,95%CI=1.435～4.796）;而在-1722位点的基因型频率、等位基因频率与对照组比较差异无统计学意义（P＞0.05）.结论CTLA-4基因启动子区-1661位点G等位基因与中国汉族UC存在显著相关性.