MTHFR基因多态性与老年人脑梗死的相关性研究

目的　探讨N5,N10 亚甲基四氢叶酸还原酶 (MTHFR)基因多态性与老年人脑梗死的相关性及预后分析。　 方法　应用多聚酶链反应 限制性内切酶片段长度多态性技术 (PCR RFLP)对 90例老年性脑梗死 (脑梗死组 )和 10 1例正常老年人 (对照组 )进行MTHFR基因多态性分析并进行基因型及等位基因频率计数。　 结果 　脑梗死组TT型基因频率及T等位基因频率分别为 2 6 7%和 49 4% ,对照组分别为 12 8%和 44 0 % ,经 χ2 检验 ,2组间有统计学意义 (P <0 0 1)。　 结论　MTHFR基因多态性与老年人脑梗死有相关性     

MTHFR基因rs1801133位点多态性与脑卒中的相关性

目的 探讨5,10-亚甲基四氢叶酸还原酶(MTHFR)基因rs1801133位点多态性与脑卒中的相关性。方法 共纳入华北理工大学附属医院脑卒中患者194例(病例组),再根据脑卒中类型分为缺血性脑卒中(IS)组和出血性脑卒中(ICH)组,无脑卒中相关病史的体检者221例为对照组。收集一般资料和多项检验结果,提取空腹外周血中DNA,利用实时荧光PCR技术定性定量检测MTHFR基因rs1801133位点多态性。通过χ²检验评估CC、CT和TT 3种基因型和C、T等位基因的差异。通过多因素二元Logistic回归分析包括CT、TT两种基因型在内的共12种因素与脑卒中的关系。结果 在MTHFR基因rs1801133位点上相比较：IS组与ICH组基因型和等位基因频数无显著差异(P>0.05);但是病例组及IS、ICH组分别与对照组相比,基因型和等位基因频率差异有统计学意义(P<0.05)。在5种基因模型(等位基因模型：T vs C;显性模型：CT+TT vs CC;隐性模型：TT vs CC+CT;共显性杂合子模型：CT vs CC,共显性纯合子模型：TT vs ...     

MTHFR基因不同位点突变与维吾尔族肺癌患者生存期相关性研究

目的:探究5,10-亚甲基四氢叶酸还原酶(MTHFR)在维吾尔族肺癌患者中的表达量和MTHFR基因677C/T、1298A/C多态性分布对维吾尔族肺癌患者进程的影响。方法:前瞻性研究。选取2018年9月至2020年9月在新疆喀什地区第一人民医院收治的维吾尔族肺癌患者50例为试验组,选取同期在该院体检的健康维吾尔族者50...     

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基因多态性与老年慢性肾衰竭的相关性

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与老年慢性肾衰竭(CRF)的相关性。方法 268例老年CRF患者为CRF组。另外选取同期健康体检人群250例为对照组。采用PCR基因芯片技术检测MTHFR C677 C/T基因多态性。CRF组每日口服叶酸、维生素B6和维生素B12治疗6个月。治疗前后,采集患者静脉血2 ml,检测同型半胱氨酸(Hcy)和肌酐(Scr),计算得到eGFR。结果 CC、CT和TT型基因频率在两组间差异有统计学意义(P<0. 05); CRF组T等位基因频率显著高于对照组(P<0. 05)。治疗前,MTHFR基因TT型血清Hcy水平显著高于CC、CT型(均P<0. 05),eGFR显著低于CC、CT型(P<0. 05);治疗前后血清Hcy水平和eGFR差值均显著低于CC、CT型(均P<0. 05)。MTHFR基因TT型心绞痛、心肌梗死、心力衰竭和总体心血管事件发生率显著高于CC、CT型(均P<0. 05)。结论 MTHFR T等位基因可能是武汉市老年人群发生CRF的一个易感基因,MTHFR基因TT型患者肾功能更差,叶酸补充治疗效果不佳。     

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。     

MTHFR基因多态性及血浆同型半胱氨酸与老年脑梗死的相关性研究

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）与老年脑梗死的相关性。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102例老年脑梗死患者（脑梗死组）和100例健康老年人（对照组）的血浆Hcy浓度及MTHFR基因型。结果两组MTHFR677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）;脑梗死组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型均为老年脑梗死的高危因素。     

MTHFR基因多态性与河南中部地区汉族人群急性冠脉综合征发生的关联性研究

目的探讨5,10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性与河南中部地区汉族人群急性冠脉综合征(ACS)发生的关联性。方法招募河南中部地区汉族ACS患者280例作为观察组,选取同期行健康体检的河南中部地区汉族健康受试者286名作为对照组。采用荧光染色原位杂交技术检测两组MTHFR基因C677T、A1298C位点基因型,比较两组受试者各基因型及等位基因分布的差异,采用二元Logistic回归分析MTHFR基因多态性与ACS发生的关联性。结果两组各基因型分布频率均符合Hardy-Weinberg平衡(P0.05)。对照组MTHFR C677T位点CC、CT、TT型分布频率分别为31.82%、47.90%、20.28%,MTHFR A1298C位点AA、AC、CC型分布频率分别为73.78%、21.68%、4.54%;观察组MTHFR C677T位点CC、CT、TT型分布频率分别为16.43%、40.71%、42.86%,MTHFR A1298C位点AA、AC、CC型分布频率分别为69.29%、27.14%、3.57%。两组受试者MTHFR C677T各基因型分布频率及等位基因频率比较差异有统计学意义(P0.05),而MTHFR A1298C各基因型分布频率及等位基因频率比较差异无统计学意义(P0.05)。二元Logistic回归分析显示,MTHFR C677T基因型是ACS发生的影响因素(P0.05),以TT型为参照,CC型发生ACS的可能性是TT型的24.4%,CT型发生ACS的可能性是TT型的40.2%。结论 MTHFR基因多态性与河南中部地区汉族人群ACS发生有关,其中C677T位点突变可能是ACS发生的影响因素,而A1298C位点基因多态性与ACS发生的关联性较低。     

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。     

NEDD4基因多态性与瘢痕妊娠关联性研究

目的研究NEDD4基因多态性与瘢痕妊娠的关联性。方法选择2018-01～2019-09在该院就诊的40例孕妇为研究对象,根据超声结果分为瘢痕妊娠组和非瘢痕妊娠组,每组20例。抽取肘静脉血,提取DNA样本。对NEDD4基因的rs2271289、rs2303579、rs10518830位点进行测序。比较两组基因型及等位基因频率。结果 rs2271289位点的基因型及等位基因频率在两组间比较差异有统计学意义(P 0. 05);与rs2271289位点TT基因型相比,CC基因型是促进瘢痕妊娠发生的危险因素(OR=24. 00,95%CI:1. 74～330. 80);与rs2271289位点T等位基因相比,C等位基因是促进瘢痕妊娠发生的危险因素(OR=3. 12,95%CI:1. 25～7. 78)。rs2303579和rs10518830位点的基因型及等位基因频率在两组间比较差异无统计学意义(P 0. 05)。结论 NEDD4基因rs2271289位点的CC基因型及C等位基因可能是促进瘢痕妊娠发生的危险因素。     

动脉粥样硬化性脑梗死的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 (MTHFR)基因C6 77T多态性与动脉粥样硬化性脑梗死的关系。方法　采用聚合酶链式反应和限制片断长度多态性 (PCR RFLP)技术 ,检测 6 2例动脉粥样硬化性脑梗死患者和 79名健康对照者的C6 77T突变的基因型。结果　MTHFR基因C6 77T突变型等位基因 (V)频率在患者组和对照组间比较 ,差异有显著性意义 (χ2 =4.41,P <0 .0 5 ) ;3种基因型频率在两组人群中差异均无显著性意义。基因型频率的相对危险分析 ,AV基因型比AA基因型患脑梗死的危险高 1.76倍 ;VV基因型比AA基因型患脑梗死的危险高 3.2 5倍。结论　MTHFR基因C6 77T突变型等位基因与动脉粥样硬化性脑梗死有一定的关联 ,突变基因型增加了动脉粥样硬化性脑梗死的发病危险     

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.     

MTHFR gene polymorphism and diabetic retinopathy

Diabetic retinopathy (DR) is the leading cause of catastrophic loss of vision. Each year, DR darkens the lives of 12,000 to 24,000 diabetic patients in the United States, and more than 4,000 patients in Japan. Clinically, hyperglycemia induces proliferative changes in DR synergistically with other risk factors for vascular diseases. Methyl- enetetrahydrofolate reductase (MTHFR) is an enzyme involved in remethylation of homocysteine to methionine. A polymorphic mutation (C677T) in the MTHFR gene leads to impaired enzyme activity, resulting in hyper- homocysteinemia as an independent risk factor for macroangiopathy. Recently, more and more attention has been paid to the involvement of hyperhomocysteinemia in the progression of DR, a serious microangiopathic complication of diabetes. Clinical studies have demonstrated that MTHFR gene polymorphism can contribute to the progression of DR, especially in the patients with blood glucose poorly controlled. Furthermore, accumulating evidence suggests that homocysteine activates vascular inflammation through inflammatory cytokines, including VEGF. These data imply that the decrease in plasma homocysteine could prevent the development and progression of DR. We also propose the possibility of personalized medicine for diabetes mellitus based on a better understanding of MTHFR gene polymorphism and its ramifications, which might cast new light on diabetic retinopathy.     

Correlation between arterial blood pressure and oxygenation in tetralogy of fallot

To examine the relationship between arterial blood pressure and oxygenation in patients undergoing complete surgical correction of tetralogy of Fallot, a retrospective study of 16 patients was first performed, looking at the correlation between mean arterial blood pressure (MAP) and arterial oxygen tension (PaO₂ The correlation between phenylephrine-induced changes in MAP (Δ MAP) and those in PaO₂ (Δ PaO₂ was investigated prospectively in seven patients. In the retrospective study, there was a significant correlation between MAP and (PaO₂ (n = 66; r = 0.55; P < 0.01), and most data points with a PaO₂ <50 mm Hg were associated with a MAP <60 mm Hg. In the seven patients who received phenylephrine, 10 μg/kg, a significant correlation was found between Δ MAP and Δ (PaO₂ (n = 10; r = 0.95; P < 0.01). These results suggest that in tetralogy of Fallot arterial blood pressure is a determinant of arterial oxygenation, and that the risk of serious hypoxia is significant when MAP is <60 mm Hg.     

血浆同型半胱氨酸水平亚甲基四氢叶酸还原酶基因多态性与强直性脊柱炎的相关性研究

目的 探讨血浆同型半胱氨酸(Hcy)水平与强直性脊柱炎(AS)间的联系,分析AS患者MTHFR基因C677T突变的多态性,并探讨MTHFR基因多态性与AS的相关性.方法 运用酶联免疫吸附试验(ELISA)测定100例AS患者及60名健康志愿者血浆Hcy浓度,应用多聚酶链反应-限制性内切酶片段长度多态性(PCR-RELP)分析MTHFR基因的多态性.结果 AS患者血浆Hcy浓度明显高于对照组,两组间差异有统计学意义(P＜0.01);AS组T/T型、C/T型、C/C型基因频率分布及T、C等位基因频率与对照组比较差异无统计学意义(P＞0.05);AS组T/T基因型突变的比例与对照组比较差异有统计学意义(P＜0.05);AS组和对照组T/T型的血浆Hcy水平明显高于C/T型和C/C型(P＜0.01).Logistic回归分析显示高Hcy血症是AS发病的独立危险凶素(P＜0.01,OR=4.582,95%CI=1.984～10.585).结论 AS患者血浆Hcy浓度明显高于健康志愿者,高Hcy血症是AS发病的独立危险因素.MTHFR基因T/T型突变是血浆Hcy浓度升高的一个重要影响机制,MTHFR基因T/T型突变可能与AS的发生有相关性.     

Lack of association between the MTHFR (C677T) polymorphism and atopic disease

Background: Impaired folate metabolism has been suggested as a potential risk factor for the development of asthma and atopic disease. However, there have been conflicting reports on the potential association between atopic disease and a common polymorphism of the methylene‐tetrahydrofolate reductase (MTHFR)‐gene, a well‐known marker of impaired folate metabolism. Objectives: The aim of this study was to investigate the association between the MTHFR (C677T) polymorphism and different outcome variables of asthma and atopic disease. Methods: This study was a population‐based study of 1189 participants aged 15–77 years living in Copenhagen, the Capital of Denmark. Examinations included measurements of specific IgE and skin prick tests against inhalant allergens, metacholine bronchial hyper‐reactivity, and serum eosinophilic cationic protein, and a self‐administered questionnaire about diagnoses and symptoms of allergy and asthma. In addition, participants were genotyped for the MTHFR (C677T) polymorphism. Results: None of the examined outcomes were significantly associated with the MTHFR (C677T) polymorphism. Conclusions: The results of this study using detailed objective markers of atopic disease do not support the hypothesis that impaired folate metabolism as reflected by the MTHFR genotype is involved in the development of atopic disease. Please cite this paper as: Thuesen BH, Husemoen LLN, Fenger M and Linneberg A. Lack of association between the MTHFR (C677T) polymorphism and atopic disease. The Clinical Respiratory Journal 2009; 3: 102–108.     

No association between MTHFR gene polymorphism and diabetic nephropathy in Japanese type II diabetic patients with proliferative diabetic retinopathy

The development of diabetic nephropathy shows marked variation among individuals. Not only hyperglycemia, but also genetic factors may contribute to the development of diabetic nephropathy. Methylenetetrahydrofolate reductase (MTHFR) is involved in remethylation of homocysteine to methionine. Decreased activity of MTHFR which can result in hyperhomocysteinemia may lead to cerebrovascular disease and coronary artery disease. Recently, a common C to T mutation at nucleotide position 677 of the MTHFR gene (MTHFR677C>T) has been reported to be correlated with hyperhomocysteinemia and the severity of coronary artery disease as macroangiopathy. In the present study, we recruited 173 of Japanese type II diabetic patients with proliferative diabetic retinopathy who would be exposed to long-term hyperglycemia, and examined the contribution of the MTHFR gene polymorphism to the development of diabetic nephropathy as microangiopathy. The frequency of the mutated allele was 43.3% in patients with nephropathy (n = 105) versus 41.9% in those without nephropathy (n = 68). The genotype frequencies were +/+, 16.2%; +/−, 54.3%; −/−, 29.5% in patients with nephropathy versus +/+, 13.2%; +/−, 57.4%; −/−, 29.4% in those without nephropathy (+ indicates the presence of the mutation). The MTHFR genotype and allele frequencies were not significantly different between patients with and without nephropathy. Therefore, we conclude that the MTHFR gene polymorphism is not associated with the development of diabetic nephropathy in Japanese type II diabetic patients.