MTHFR C677T基因多态性与缺血性脑血管病的相关性

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与缺血性脑血管病的相关性。方法:运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对512例缺血性脑血管病患者和500例健康对照者进行MTHFR C677T基因多态性分析。结果:缺血性脑血管病患者中突变纯合子TT基因型频率为40%,突变杂合子CT基因型频率42·6%,野生型CC基因型频率为17·4%;对照组中TT基因型频率为32·8%,CT基因型频率为34·6%,CC基因型频率为32·6%;患者组和对照组T等位基因频率分别为61·3%和51·1%,C等位基因频率分别为38·7%和49·9%,以上各频率之间均有显著性差异(P<0·05)。结论:MTHFR C677T基因多态性与缺血性脑血管病的发生有一定关系,可能是缺血性脑血管病的一个重要危险因素。     

MTHFR C677T基因多态性与老年H型高血压患者肾损害的关系

目的 探讨亚甲基四氢叶酸还原酶(MTHFR C677T)基因多态性与老年H型高血压患者肾损害的相关性。方法 198例老年H型高血压患者根据是否合并肾损害分为高血压肾损害(HRD)组(n=75)和单纯高血压(HNRD)组(n=123),另选取同期体检的老年非高血压患者作为对照组(n=40)。收集各组临床资料;采用实时定量聚合酶(RT-PCR)法进行各组MTHFR C677T基因型的测定,利用Logistic回归模型分析老年H型高血压患者发生肾损害的影响因素。结果 HRD组及HNRD组CC基因型频率明显低于对照组(P<0.05);且HRD组CC基因型频率明显低于HNRD组,CT基因型频率明显高于HNRD组(P<0.05)。HRD组、HNRD组和对照组C等位基因及T等位基因分布频率组间差异均有统计学意义(P<0.05)。多因素Logistic回归分析显示,MTHFR C677T基因T等位基因(OR=2.147,95%CI:1.347～3.423)是H型高血压患者发生肾损害的独立影响因素(P<0.05)。结论 MTHFR C677T基因多态性与老年H型高血压患者肾损害的...     

MTHFR基因C677T多态性与大肠癌组织中P-gp表达的相关性

目的探讨亚甲基四氢叶酸还原酶（MTHFR）基因C677T多态性与P-gp在大肠癌中表达的关系。方法采用免疫组化SP法检测68份大肠癌组织中P-gp的表达情况,分析其与大肠癌病理特征的关系;抽取其化疗前静脉血2 ml,提取白细胞DNA,采用PCR-RFLP技术检测MTHFR基因C677T基因型。结果大肠癌组织p-gp阳性率为47.1%,其表达与大肠癌分化程度、临床分期及淋巴结转移均无明显相关性。68例患者中,MTHFR C/C基因型27例,其P-gp的阳性率为51.9%;C/T基因型29例,P-gp阳性率为58.6%;T/T基因型12例,其P-gp阳性率为8.3%。T/T基因型患者P-gp阳性率显著低于C/C基因型（P=0.01）和C/T基因型患者（P=0.003）,C/C基因型和C/T基因型患者P-gp阳性表达率无统计学意义。结论大肠癌组织中P-gp表达与MTHFR基因C677T T/T基因型呈负相关;其可作为早期预测大肠癌患者化疗敏感性的指标。     

类风湿关节炎亚甲基四氢叶酸还原酶基因多态性与甲氨蝶呤疗效和不良反应的关系

目的 探讨类风湿关节炎(RA)患者亚甲基四氢叶酸还原酶(MTHFR)基因677CDT[rs1801133)、1298A/C(rs1801131)单核苷酸多态性(SNP)及其与甲氨蝶呤(MTX)治疗的疗效和不良反应相关性.方法 收集RA患者184例.分为单用MTX组、MTX联用其他改善病情抗风湿药(DMARD)组、非MTX的DMARD组,于治疗前及治疗后24周检查临床及实验室指标,评价疗效及不良反应.采用实时荧光定量聚合酶链反应(FQ-PCR)方法检测RA患者及100名健康对照组的MTHFR基因677C/T及1298A/C多态性,比较两组间基因型分布及等位基因频率.结果 677CC/CT/TT基因型分布在RA组(19%、67%、14%)与健康对照组(27%、56%、17%)基因型分布频率差异无统计学意义(P>0.05);1298AA/AC/CC基因型分布在RA组(66%、31%、3%)健康对照组(70%、30%、0%)基因型分布频率差异无统计学意义(P>0.05).677CC/CT/TT基因型分布在RA有心血管并发症组(6%、75%、19%)与正常对照组(27%、56%、17%)差异有统计学意义(P<0.05).在单用MTX治疗者巾,1298AA/AC/CC在MTX治疗有效组(54%、44%、2%)和无效组(90%、10%、O%)中差异有统计学意义(P<0.05),677CC/CT/TT在MTX有不良反应组(13%、71%、16%)和无不良反应组(48%、48%、4%)中差异有统计学意义(P<0.05).在MTX联用其他DMARD组,677CC/CT/TT在有不良反应组(9%、78%、13%)和无不良反应组(35%、50%、15%)中差异有统计学意义(P<0.05).结论 MTHFR基因677C/T及1298A/C多态性与RA发病无关;677 C/T多态性与RA心血管并发症的出现有关、与MTX治疗后的不良反应相关,1298 A/C多态性与MTX的疗效相关.     

MTHFR C677T基因多态性与新疆哈族和汉族食管癌易感性的关系

目的:探讨亚甲基四氢叶酸还原酶(MTHFR) 基因C677T多态性与新疆哈族、汉族食管癌易感性的关系．方法:用PCR-RFLP方法检测食管癌患者178 例(哈萨克族94例,汉族84例)和同一地区无肿瘤病史的正常对照者155例(哈萨克族98例,汉族57例)的MTHFR基因C677T基因型分布．结果:新疆哈族食管癌组中MTHFR C677T 3种基因型CC,CT,TT,所占比例分别是 56．4％,36．2％,7．4％,与新疆汉族食管癌组中的32．9％,40．0％,27．1％相比,存在显著差异(X2=1 5．37,P<0．05);哈族正常对照组分别为58．2％,29．6％,12．2％与汉族正常对照组 22．8％,52．6％,24．6％相比,有显著差异(X2= 18．26,P<0．05)．MTHFR 3种基因型在哈族食管癌组中的分布(CC 56．4％,CT 36．2％and TT 7．4％)与对照组中(CC 22．8％,CT 52．6％and TT 24．6％)相比,无显著差异(X2=1．776,P= 0．412)．在汉族食管癌组与对照组间也无显著差异(X2=2．750,P=0．253)．结论:MTHFR C677T基因多态性分布在新疆哈族、汉族正常对照组间存在民族差异,在食管癌间也存在差异．MTHFR C677T基因多态性可能与新疆哈萨克族与汉族食管癌的易感性无关．     

广西红水河流域长寿人群MTHFR C677T 基因多态性与血脂水平的相关性

目的 探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T位点的多态性与广西红水河流域长寿人群的血脂水平及长寿的关系.方法 应用聚合酶链反应—限制性片段长度多态性(PCR-RFLP)方法对505例该流域90岁以上壮族长寿老人(长寿组)、普通健康壮族中老年人468例(非长寿组)进行基因分型,并检测血压、体质指数、血脂(TC、TG、HDL、LDL)等指标.结果 长寿组和对照组C、T等位基因频率分别为80.2％、19.8％和85.0％、15.0％;两组3种基因型(CC、CT、TT)频率分别为65.5％、29.3％、5.2％和73.9％、22.2％、3.8％;等位基因及基因型频率在两组间差异显著,且有T等位基因在长寿组女性中富集现象,而男性中无此趋势.在血脂水平上除HDL外,长寿组的TC、TG、LDL水平显著高于非长寿组(P＜0.01).进一步按MTHFR C677T基因型和性别分层后发现,长寿组中女性突变基因型(CT/TT)的TC、TG及LDL水平明显高于非突变基因型(CC);而男性各血脂水平分别在两组3种基因型间未发现有明显差异.结论 MTHFR基因C677T位点的多态性与血脂水平及长寿有一定的关系,并呈性别特异性,可能是红水河流域长寿现象的分子遗传学基础之一.     

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。     

MTHFR基因多态性与冠心病的关系

目的研究天津地区人群N^5,N^10-亚甲基四氢叶酸还原酶（MTHFR）基因C677T多态性与冠心病的关系。方法应用聚合酶链反应（PCR）技术和限制性酶切片段长度多态性（RFLP）分析技术检测50例冠心病患者（冠心病组）和50例正常人（对照组）的MTHFR基因C677T多态性,应用高效液相色谱法测定血浆同型半胱氨酸（Hcy）水平,采用125I标记放免法测定血清叶酸浓度。结果1.冠心病组与对照组MTHFR基因频率分布不同（P〈0.05）,对照组CC型、TC型、TT型基因频率分别为52.0%,28.0%,20.0%,冠心病组分别为26.0%,44.0%,30.0%。冠心病组T等位基因频率为52.0%,C等位基因频率为48.0%,与对照组比较有显著性差异（P〈0.05）。2.两组的TT基因型者血浆Hcy浓度均明显高于CC和TC基因型者（P〈0.05）,而后两者间无显著性差异（P〉0.05）。3.冠心病组Hcy浓度高于照组（P〈0.05）,两组叶酸水平无显著性差异（P〉0.05）,血浆Hcy浓度与叶酸水平呈显著负相关（r分别为-0.617和-0.588,P〈0.05）。结论MTHFR基因C677T点突变与冠心病发病密切相关,MTHFR基因纯合突变是引起高Hcy血症的一个重要的遗传因素。     

Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene

BACKGROUND: There is an association between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and methotrexate related toxicity. OBJECTIVE: To examine the relations between the recently described A1298C polymorphism of the MTHFR gene, plasma homocysteine, methotrexate toxicity, and disease activity in patients with rheumatoid arthritis. DESIGN: A cross sectional study on 93 methotrexate treated patients with rheumatoid arthritis, comprising a clinical interview and physical examination to determine disease activity and methotrexate related adverse reactions. Genotype analysis of the MTHFR gene was carried out and fasting plasma homocysteine and serum folate concentrations were measured. The data were analysed using univariate analysis. Allele and genotype distributions were compared with those of a healthy control group. RESULTS: The frequency of the 1298CC genotype (24.7%) in the rheumatoid study group was greater than expected in the general population (12.8%, p<0.001). This genotype was associated with a significantly low rate of methotrexate related side effects. The odds ratio for side effects in patients with wild type 1298AA genotype v 1298CC genotype was 5.24 (95% confidence interval, 1.38 to 20). No correlation of disease activity variables or plasma homocysteine with MTHFR A1298C and C677T polymorphisms was observed. CONCLUSIONS: 1298CC polymorphism was more common in methotrexate treated rheumatoid patients than expected in the population, and was associated with a reduction in methotrexate related adverse effects. The A1298C polymorphism of the MTHFR gene may indicate a need to adjust the dose of methotrexate given to patients with rheumatoid arthritis.     

肝硬化高同型半胱氨酸血症与MTHFR基因C667T多态性的关系

目的研究肝硬化血浆同型半胱氨酸(HCY)水平及其与N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性的关系.方法采用柱前衍生化-HPLC方法检测112例健康对照者、87例肝硬化患者血浆同型半胱氨酸的水平,用多聚酶链反应-限制性内切酶片断长度多态性技术(PCR-RFLP)检测其MTHFR基因C667T多态性.结果健康对照组平均血浆HCY浓度为(8.34±3.59)μmol/L,肝硬化组平均血浆HCY浓度为(21.71±4.85)μmol/L.与健康对照组相比,肝硬化组血浆HCY水平显著升高,差异有统计学意义(P＜0.01).PCR-RFLP检测结果发现MTHFR基因型有3种,即纯合子突变TT(+/+)型,杂合子突变TC(+/)型,正常CC(-/-)型.肝硬化组中+/+型、+/型和/-型频率分别为29.9%、52.9%、17.2%;健康对照组分别为19.6%、33.9%、46.4%,两组差异有统计学意义.肝硬化组MTHFR基因突变无论是纯合子还是杂合子突变基因型,其血浆HCY水平均明显高于正常基因型.结论高同型半胱氨酸血症可能是肝硬化的一个危险因素,血浆HCY水平可作为肝硬化的一个辅助诊断指标,MTHFR基因C667T多态性可能是肝硬化高同型半胱氨酸血症的易感基因之一.     

Association of the MTHFR C677T and A1298C polymorphisms with methotrexate toxicity in rheumatoid arthritis: a meta-analysis

The aim of this study was to explore whether the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) play a role in methotrexate (MTX) toxicity in rheumatoid arthritis (RA). MEDLINE and EMBASE database searches and subsequent manual searches were utilized to identify articles in which C677T and A1298C MTHFR polymorphisms were evaluated in RA patients taking MTX. A meta-analysis was conducted to identify associations between MTHFR polymorphisms and MTX toxicity. Twelve studies comprising a total of 2,288 RA patients were included in our meta-analysis. Meta-analysis revealed an association between the overall toxicity of MTX and the MTHFR 677TT genotype (odds ratio [OR]?=?1.615, 95 % confidence interval [CI]?=?1.185–2.200, p?=?0.002). Stratification by ethnicity indicated an association between the MTHFR 677TT genotype and the overall toxicity of MTX in East Asians (OR?=?1.583, 95 % CI?=?1.075–2.331, p?=?0.020). The toxicity of MTX also was found to be associated with the TT genotype in patients taking folate (OR?=?1.893, 95 % CI?=?1.283–2.793, p?=?0.001). Stratification by toxicity type indicated an association between the MTHFR 677TT genotype and any adverse effects (OR?=?1.716, 95 % CI?=?1.127–2.612, p?=?0.012). Meta-analysis stratified by toxicity type indicated an association between the MTHFR 1298CC genotype and any adverse effects (OR?=?0.501, 95 % CI?=?0.284–0.886, p?=?0.017). The results of our meta-analysis suggest that the MTHFR C677T and A1298C polymorphisms are associated with MTX toxicity in RA patients.     

Association between MTHFR C677T and A1298C gene polymorphisms and maternal risk for Down syndrome: A protocol for systematic review and/or meta-analysis

Background:Down syndrome (DS) is one of the most common chromosomal abnormalities among live-born babies and one of the best-known intellectual disability disorders in humans. Errors leading to trisomy 21 are primarily arising from defects in chromosomal segregation during maternal meiosis (about 88% of cases), and the focus of many investigations has been to identify maternal risk factors favoring chromosome 21 malsegregation during oogenesis. Maternal polymorphisms of genes required for folate metabolism are the most investigated risk factors for the birth of children with DS. Through this review, we sought to investigate the association of the polymorphisms “C677T” and “A1298C” of the MTHFR gene with maternal risk for DS.Methods:We will use the databases PubMed, Embase, Scopus and Web of Science to search for case-control studies published from 1999 up to September 2021 without language restriction. Results will be presented as relative risks and 95% confidence intervals for dichotomous outcomes and mean differences, or standardized mean differences along with 95% confidence intervals, for continuous outcomes. The all data synthesis will be analyzed on the Review Manager 5.2 version software.Results:This study will be able to clarify all the doubts we seek and that it will be able to provide accurate data that will be able to describe how these polymorphisms can act to increase the predisposition for the birth of children with DS in different populations and under different dietary conditions.Conclusions:This study will clarify the relationship between C677T and A1298C polymorphisms MTHFR gene with increased the maternal risk for Down syndrome.Registration:This systematic review and meta-analysis protocol has been registered on the Prospective Registry of International Systematic Review and Meta-analyses: CRD42021269338.     

Relationship between genetic polymorphism of MTHFR C677T and lower extremities deep venous thrombosis

Objective: To investigate the association between the polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and the formation of lower extremities deep venous thrombosis, and to evaluate the etiology of deep venous thrombosis.

Methods: Polymorphisms of the 677th site C/T in MTHFR gene for 101 patients with lower extremities deep venous thrombosis (DVT group) and 120 healthy subjects (control group) were detected by polymerase chain reaction with sequence-specific primers. Genotype and allelic frequencies were compared between the two groups.

Results: Genotype frequencies of CC, CT and TT in MTHFR C677?T were 41.58, 25.74 and 32.67% in DVT group, and 58.33, 23.33 and 18.33% in control group, respectively. There was a significant difference in TT genotype frequency between the two groups (P <0.05).

Conclusion: The frequency of MTHFR 677TT genotype may be correlated with the morbility of DVT.     

Infliximab versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a preliminary study from China

Aim: To report the efficacy and safety of infliximab in the treatment of active rheumatoid arthritis (RA) in Chinese patients. Methods: This is a multicentre double‐blind placebo controlled study. Patients with active RA despite being on a stable dose of methotrexate were randomly assigned to receive either infliximab 3 mg/kg body weight or placebo infusion at weeks 0, 2, 6 and 14. All patients continued their stable dose of methotrexate throughout the study. Patients were assessed at weeks 0, 2, 6, 14 and 18 for the American College of Rheumatology (ACR) 20%, 50% and 70% response (ACR20, 50 and 70, respectively). Health assessment questionnaire (HAQ), erythrocyte sedimentation rate (ESR), c‐reactive protein (CRP), duration of morning stiffness and adverse effects were monitored. Results: Infliximab was effective in improving the disease activity of RA with significant ACR20 response observed at week 2 (infliximab vs. placebo 52.87%vs. 13.95%, P < 0.05). Significant differences in the ACR20 and ACR50 response rates between the two treatment groups were also observed at week 18 (75.86% and 43.68% of patients receiving infliximab vs. 48.84% and 25.58% and 13.95% of patients on placebo, P = 0.0003 and P = 0.011, respectively). Infliximab was generally well tolerated. The rate of adverse events and withdrawal due to adverse events were similar between the two groups. Most adverse reactions were transient. One patient in the infliximab group developed tuberculosis during the study. One patient in the placebo group developed antinuclear antibodies without obvious signs of systemic lupus erythematosus. Conclusion: In this preliminary study, infliximab infusions, at a dose of 3 mg/kg body weight given at various intervals over 14 weeks, were effective in controlling the signs and symptoms of active RA in Chinese. Infliximab also appeared to be well tolerated. Further studies involving a larger number of patients over a more prolonged period will further evaluate the long‐term efficacy and safety of infliximab in this group of patients.     

急性脑梗死患者MTHFR基因多态性与血浆同型半胱氨酸水平的关系

目的 探讨急性脑梗死（ACI）患者N5,N10-亚甲四氢叶酸还原酶（MTHFR）基因多态性与血浆同型半胱氨酸（Hcy）水平的关系.方法 采用多聚酶链反应2-限制性内切酶片段长度多态性技术（PCR2-RFLP）检测48例ACI患者MTHFR基因C677T位点多态性,同时测定血浆总Hcy及血清叶酸、维生素B12、尿酸（UA）.结果 ACI患者MTHFR基因T/T型频率为35.43％,T/C型频率为56.32％,C/C型频率为8.25％;T等位基因频率为63.59％,C等位基因频率为36.41％.MTHFR基因T/T型ACI患者血浆Hcy显著高于其他两型,T/C型与C/C型血浆Hcy水平较比较无显著差异.Hcy中度与轻度增高者MTHFR基因分布比较,P≤0.05.3组基因型间叶酸、维生素B12及UA水平均无显著差异.结论 ACI患者MTHFR基因C677T突变与Hcy水平显著相关,MTHFR基因纯合突变可能是引起高Hcy的一个重要遗传因素.