高同型半胱氨酸血症与血管性痴呆相关性研究

目的:探讨血浆同型半胱氨酸(Hcy)水平与血管性痴呆(VD)的相关性。方法:应用全自动生化分析仪用循环酶法检测37例VD患者的血浆Hcy浓度,并与39例非痴呆脑梗死患者作为同龄对照组血浆Hcy浓度进行比较,同时测定血浆叶酸及VitB12浓度,根据简易精神状态检查量表(MMSE)评分划分VD患者严重程度,分为轻度(20～24分),中度(10～19分),重度(10分以下)。结果:VD组血浆Hcy水平显著高于非痴呆脑梗死组(P<0.05),VD组血浆叶酸水平显著低于非痴呆脑梗死组(P<0.05),两组间VitB12水平无显著性差异(P>0.05),不同程度VD患者血浆Hcy、叶酸水平有显著性差异(p<0.05),VitB12水平无显著性差异(p>0.05)。结论:高同型半胱氨酸血症可能是VD发病的一个新的危险因素。     

MTHFR基因C677T位点突变及高同型半胱氨酸血症和血管性痴呆的发生相关性

目的研究血浆同型半胱氨酸(Hcy)浓度及亚甲基四氢叶酸还原酶(MTHFR)基因多态性与血管性痴呆(VaD)的关系。方法选取83例VaD患者作为观察组和81例非痴呆脑梗死患者作为对照组,分别测定两组患者的MTHFR基因多态性、Hcy浓度、维生素B12和叶酸水平,根据简易精神状态检查量表(MMSE)评定VaD患者痴呆程度,对指标进行比较和相关性分析。结果 MTHFR基因TT纯合子在观察组VaD患者的分布频率明显高于对照组,差异具有统计学意义(P0.05);两组患者的MTHFR基因C、T等位基因分布频率差异具有统计学意义(P0.05)。观察组VaD患者的血浆Hcy浓度明显高于对照组,其血清叶酸与维生素B12浓度明显低于对照组,VaD患者的血浆Hcy水平随着痴呆程度的增加而明显提高,差异均具有统计学意义(P0.05)。VaD患者血浆Hcy水平与自身痴呆程度呈正相关(r=0.452,P0.05),与MMSE评分呈负相关(r=-0.246,P0.05)。结论MTHFR基因C677T突变及高水平Hcy与VaD的发生、发展相关,高Hcy血症是VaD发病的一个重要因素。     

MTHFR基因多态性及血浆同型半胱氨酸水平与中青年人脑梗死的关系

目的探讨N5、N10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T位点突变和血浆总同型半胱氨酸(tHcy)水平与中青年脑梗死发病的关系。方法对140例研究对象采用多聚酶链反应-限制性内切酶片段长度多态性技术),检测MTHFRC667T基因型,用高效液相色谱法测定血浆总同型半胱氨酸水平,同时所有研究对象记录其病史、体检及一些实验室检查资料。结果脑卒中患者MTHFR基因纯合子突变(T)和杂合子突变(CT)发生率(76.3%)明显高于对照组(55.0%,P=<0.05),卒中组T等位基因频率(55.05%)也高于对照组(37.5%,P<0.05);脑梗死患者血浆总同型半胱氨酸水平及异常检出率明显高于对照组(P<0.001)。Logistic回归分析结果显示:在调整传统危险因素后,升高的Hcy水平和中青年脑梗死发病有关。结论高同型半胱氨酸血症是中国中青年人群中脑梗死发病的一个重要的独立危险因素,而MTHFR基因C677T位点突变可能是高同型半胱氨酸的重要遗传因素,可能和其它危险因素等存在交互作用。     

脑梗死患者与其血浆同型半胱氨酸水平及MTHFR基因关系的研究

目的探讨脑梗死(CI)患者与其血浆同型半胱氨酸(homocystine,HCY)水平及N5+10-亚甲基四氢叶酸还原酶(MTHFR)基因的关系.方法应用高效液相色谱仪和电化学检测法测定1998-02-2001-02收治的84例CI患者和78名正常老年人血浆总HCY水平,运用多聚酶链反应-限制性内切酶片段长度多态性技术(PCR-RFLP)检测MTHFR基因多态性,同时测定血浆叶酸及维生素B12水平.结果CI患者血浆总HCY水平显著高于正常对照组MTHFR基因型有3种,即纯合子(T/T)型、杂合子(T/C)型、纯合子(C/C)型.3组基因型和等位基因频率相比,差异均无显著性;CI组血浆叶酸及维生素B12水平明显低于正常对照组(P＜0.05).结论高HCY血症可能是CI患者发病的一个新危险因素.     

高同型半胱氨酸血症与脑卒中相关性研究

目的探讨血浆同型半胱氨酸(H cy)水平对脑卒中临床亚型、复发及痴呆的影响,并研究高同型半胱氨酸血症(HH)与脑卒中传统危险因素之间的相关性。方法应用酶联免疫吸附试验(EL ISA)检测90例急性脑卒中患者血浆H cy水平。将研究对象分为不同临床亚型,脑白质损伤组与非脑白质损伤组,青年组与老年组,痴呆组与非痴呆组。对不同类型脑卒中患者血浆H cy水平进行比较,对HH脑卒中传统危险因素进行相关与回归分析。结果首次发作(FCS)组血浆H cy水平明显低于复发(RCS)组(P<0.01),HH发生率比较RCS组明显高于FCS组(P<0.05)。痴呆组血浆H cy水平与对照组有差别(P<0.01)。饮酒者血浆H cy含量明显高于不摄入酒精者(P<0.05)。结论HH是脑卒中的独立危险因素,脑卒中患者普遍存在HH,在复发性脑卒中患者中尤其明显。血浆H cy水平随年龄增加而增加,同时HH与血管性痴呆和/或变性性痴呆有关。     

血浆同型半胱氨酸水平与脑梗死的关系

目的探讨脑梗死与血浆同型半胱氨酸(H cy)水平的关系。方法测定400例脑梗死患者及200例同期住院既往无临床心脑血管病患者的血液总同型半胱氨酸(H cy),维生素B12和叶酸(FA)。结果血液H cy水平,脑梗死组(17.25±7.11)μm o l/L,对照组(10.48±3.01)μm o l/L,差异有显著意义(P<0.01)高同型半胱氨酸在≤40岁患者中危险因素更明显。血清tH cy水平与V itB12及FA水平呈负相关。结论血清tH cy水平升同增加脑梗死的危险度。     

亚甲基四氢叶酸还原酶基因多态性与脑梗死的关系

目的 探讨亚甲基四氢叶酸还原酶(MTHFR)基因C 677T多态性及同型半胱氨酸水平与脑梗死的关系.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测30例脑梗死患者和30例对照者的MTHFR基因C 677T多态性分布,同时应用高效液相色谱法测定血清同型半胱氨酸水平.结果 对照组基因型频率分别为53.33%、40%、6.67%;脑梗死组分别为50%、43.33%、6.67%,两组各基因型分布间差别无显著性意义(P>0.05);对照组等位基因频率分别为73.33%、26.67%,脑梗死组分别为71.66%、28.34%,两组等位基因的分布间差别无显著性意义(P>0.05).脑梗死组血清半胱氨酸水平高于对照组,差异有显著性(P<0.05).结论 本研究未发现MTHFR基因C677T多态性与脑梗死之间存在相关关系,而高同型半胱氨酸血症可能是脑梗死的危险因素.     

MTHFR基因多态性及同型半胱氨酸与青年脑血管病的关系

目的:研究Ns,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)水平与青年脑血管病的关系。方法:研究对比40例青年脑血管病患者(首次发病年龄≤50岁)及32例健康青年人的MTHFR基因多态性及血浆Hcy水平。结果:(1)对照组及病例组T/T纯合子率分别为37.5％和22.5％;T等位基因频率分别为60.9％和51.3％,差异均无显著统计意义(均P>0.05)。(2)病例组血浆Hcy几何均值(11.0±2.3μmol/L)显著高于对照组(8.0±1.4μmol/L,P<0.05)。(3)所有受试者中T/T组Hcy值高于C/C组(10.4μmol/L和7.6μmol/L),但差异无显著性(P>0.05)。结合叶酸考虑,进一步将所有受试者按叶酸中位数水平分组。叶酸中位数以下组中,T/T组Hcy值显著高于C/C组(P<0.05);而叶酸中位数以上组中,T/T组Hcy值与C/C组无显著差异。(4)血浆Hcy与叶酸、维生素B12呈显著负相关,与肌酐呈显著正相关。吸烟者血浆Hcy水平显著高于不吸烟者(P<0.05)。结论:(1)本组人群MTHFR基因C677T突变的纯合子在低叶酸状态下可引起血浆Hcy水平显著增高,但与青年脑血管病无显著关系。MTHFR基因677TT纯合突变可能为健康青年人脑血管的保护因素。(2)血浆Hcy水平与青年脑血管病的发生密切相关。(3)叶酸、维生素B12肌酐、吸烟是Hcy的非遗传影响因素。     

胱硫醚β合酶基因突变及负荷后同型半胱氨酸水平与青年脑梗死

目的　研究胱硫醚β合酶(CBS)基因T833C突变对蛋氨酸负荷试验(MLT)后血浆同型半胱氨酸(Hcy)水平的影响及其对青年脑梗死的致病作用。方法　采用高压液相色谱法测定血浆空腹同型半胱氨酸(Fhcy)及负荷后同型半胱氨酸(Phcy)水平,选取Fhcy水平正常的75例青年脑梗死患者和52例正常对照者。利用扩增阻滞突变体系法检测CBST833C基因型。结果　病例组Phcy水平和负荷前后Hcy水平的差值均高于对照组;病例组和其负荷后高同型半胱氨酸血症(PHhcy)组CBS基因C/C、C/T型和C等位基因频率分别高于对照组和病例组负荷后非高同型半胱氨酸血症(NPHhcy)组;病例组、对照组和PHhcy青年脑梗死患者组CBSC/C型者Phcy水平依次高于C/T型和T/T型者;NPHhcy青年脑梗死患者CBSC/C型者Phcy水平高于T/T型者,C/T型显著高于T/T型者。结论　CBST833C基因突变可能是Phcy水平异常升高的遗传原因,并间接导致青年脑梗死发生的重要遗传危险因素。     

Hcy及MTHFR C677T基因多态性与河南汉族脑梗死的关系

目的探讨同型半胱氨酸(Hcy)水平及亚甲基四氢叶酸还原酶(MTHFR)基因多态性与河南汉族人群脑梗死的相关性。方法运用循环酶法和PCR-限制性片段长度多态性分析检测河南汉族300例脑梗死患者及261例健康对照者Hcy水平及MTHFR C677T基因型,并进行测序验证。结果病例组和对照组平均空腹血浆Hcy水平差异有显著性(P<0.01);MTHFR C677T在患者组TT型、CT型频率及T等位基因频率均显著高于对照组,差异有统计学意义(P<0.01);两组不同基因型相应的Hcy浓度差异有统计学意义(P<0.01),TT型与CT型显著高于CC型(P<0.01)。Logistic回归分析结果显示:在调整传统危险因素后,MTHFR C677T基因突变及升高的Hcy水平和脑梗死发病相关。结论血浆Hcy浓度升高是河南汉族脑梗死的独立危险因素;MTHFR C677T基因突变可影响Hcy水平,可能是脑梗死发生的重要机制之一。MTHFR基因突变可能是河南汉族人群中脑梗死发病中的一个重要危险因素。     

5,10-亚甲基四氢叶酸还原酶基因多态性与脑梗死患者颈动脉粥样硬化的相关性研究

目的探讨血浆同型半胱氨酸(homocysteine,Hcy)代谢酶5,10-亚甲基四氢叶酸还原酶(5,10-methylenetetrahydrofolate reductase,MTHFR)C677T基因多态性与脑梗死患者颈动脉粥样硬化的相关性。方法纳入新发前循环大动脉粥样硬化性脑梗死组患者,以无脑梗死的门诊体检者作为对照组。用荧光偏振免疫法测定两组血浆Hcy水平,彩色多普勒超声进行双侧颈动脉颅外段检查明确是否存在动脉粥样硬化斑块及斑块性质,采用全自动基因芯片检测目标人群MTHFR C677T基因型。结果共纳入新发前循环脑梗死组患者150例,对照组100例。①脑梗死组MTHFR C677T突变(TT)基因型及T等位基因频率显著高于对照组(48.0%vs 19.0%,χ~2=22.067,P0.001;64.0%vs 45.5%,χ~2=6.907,P=0.009);②脑梗死组MTHFR C677T C→T基因突变与颈动脉粥样硬化狭窄程度呈正相关(r=0.353,P0.001);③脑梗死组中不稳定斑块组MTHFR C677T突变(TT)基因型及T等位基因频率显著高于稳定斑块组(66.2%vs 34.1%,χ~2=14.587,P0.001;77.5%vs 60.2%,χ~2=6.978,P=0.008)。结论 MTHFR C677T位点C→T基因突变是颈动脉粥样硬化斑块不稳定性及其狭窄程度的相关危险因素。     

同型半胱氨酸及亚甲基四氢叶酸还原酶基因多态性与缺血性卒中的关系研究

目的 探讨同型半胱氨酸（homocysteine,Hcy）水平及亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR）基因多态性与缺血性卒中（ischemic stroke,IS）的关系,并分析Hcy与叶酸、 VitB12之间的相关性。 方法 运用酶循环法和聚合酶链式反应（polymerase c hain r eaction,PCR）-芯片杂交法分别检测217 例IS患者和223例对照者血浆Hcy与MTHFR C667T基因型,并对照分析两组的基因型频率和等位基因 频率分布差异及血浆Hcy水平;运用免疫分析法检测两组中既往未服用过含叶酸和VitB12药物的88例 I S患者和125例对照者血清叶酸、Vi tB12水平,并与Hcy水平进行相关性分析。 结果 IS组Hcy浓度高于对照组,差异有显著性（[ 23.95±12.13）μmol/L vs（17.31±7.20）μmol/L, t =29.61,P＜0.001],IS组与对照组MTHFR 基因型频率CC、CT、TT型分别为14.3％、44.7％、41.0％和 18.4％、48.9％、32.7％,等位基因C与T的频率分别为36.6％、63.4％和42.8％、57.2％,无显著性差 异（基因型频率：χ 2=3.59,P =0.166;基因频率：χ 2=3.52,P =0.061）。MTHFR基因TT型（162例）、CT 型（206例）和CC型（72例）的血浆Hcy水平分别为（25.19±12.53）μmol/L、（18.21±8.08）μmol/L和 （16.65±6.90）μmol/L,其中TT型显著高于CT型和CC型,CT型显著高于CC型（P 均＜0.001）。I S组和对 照组血浆Hcy水平与VitB12呈负相关（I S组和对照组分别为r =-0.431,P＜0.001和r =-0.507,P＜0.001）, 与叶酸亦呈负相关（IS组和对照组分别为r =-0.489,P＜0.001和r =-0.446,P＜0.001）。 结论 IS患者血浆Hcy水平较正常人偏高;MTHFR C667T基因突变、叶酸和VitB12水平降低是血浆Hcy 水平升高的影响因素;MTHFR C667T基因突变可能与缺血性卒中无关。     

Methylenetetrahydrofolate reductase gene polymorphisms in patients with cerebral hemorrhage

Elevated plasma total homocysteine (HCY) level is a risk factor for coronary heart disease and ischemic stroke. We investigated relationships between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, and plasma levels of HCY and folate in patients of Mongolian races who suffered from cerebral ischemia (CI, n = 42) or cerebral hemorrhage (CH, n = 20) and in the 24 age-matched controls. The incidences of both homozygous and heterozygous MTHFR gene mutations in CI (26 and 43%) and in CH (25 and 60%) were significantly higher than those in the controls (8 and 25%). Homozygous MTHFR gene mutation was associated with reduced plasma folate levels, but not with increased plasma HCY levels. Among the subjects with homozygous MTHFR gene mutation, plasma folate levels in CH was significantly lower than those in CI and controls. MTHFR gene mutation in CH was found to be as common as that in CI and was associated with reduced plasma folate levels in the both. In homozygous MTHFR gene mutation, the plasma folate level was profoundly reduced in CH as compared with CI and controls, suggesting that subjects with low plasma folate levels have a predisposition to intracerebral bleeding.     

The effect of C677T mutation of methylene tetrahydrofolate reductase gene and plasma folate level on hyperhomocysteinemia in patients with meningomyelocele

To evaluate the relationship between genotypes of methylene tetrahydrofolate reductase (MTHFR), and plasma folate and homocysteine (Hcy) levels in meningomyelocele, 21 Korean patients, 47 of their family members, and 43 healthy controls were recruited. The presence of C677T mutation in the MTHFR gene and plasma concentrations of folate/Hcy were investigated. The genotype frequency of C677T mutation was not higher in study groups (patients and family members). The plasma folate concentration showed no difference either between the study and the control groups or among MTHFR-genotypic groups. The plasma Hcy concentration in homozygotes in the study group was higher than that in the control group, and higher than that in heterozygotes when plasma folate levels were low (P=0.006). Although neither MTHFR genotype nor plasma folate/Hcy level plays a definite part on its own, they seem to have an additive effect on the occurrence of meningomyelocele. Our results support folate supplementation for the prevention of hyperhomo- cysteinemia and meningomyelocele. Received: 11 November 1999 Revised: 3 April 2000     

Mild hyperhomocysteinemia and low folate concentrations as risk factors for cervical arterial dissection

BACKGROUND AND PURPOSE: Elevated homocysteine (Hcy) plasma levels are associated with an increased risk of spontaneous cervical artery dissection (sCAD). We examined the potential association between Hcy, folate, vitamin B(12) levels and 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms in patients with cerebral infarct caused by sCAD. PATIENTS AND METHODS: 39 patients who survived a cerebral infarct caused by sCAD [20 (51%) women; 24 (61.5%) vertebral and 15 (38.5%) internal carotid arteries], and 76 healthy control subjects were included. Hcy plasma levels (fasting and after methionine load), folate and vitamin B(12) levels were measured. We also performed polymorphisms of MTHFR. Hcy, vitamin B(12), folates and polymorphisms of MTHFR were assessed and any associations were analyzed using multivariate statistics. RESULTS: Mean plasma fasting Hcy level was 9.81 mumol/l for cases and 6.38 for controls (p = 0.001). The occurrence of sCAD was associated with elevated fasting Hcy levels (>95th percentile over the control group) with an adjusted odds ratio of 7.9 (95% CI 1.66-35). The association between low plasma folate values (<5th percentile) and the presence of CAD was 7.9 (95% CI 1.6-31) after adjusting for confounding variables. The distribution of the MTHFR genotype showed a higher TT mutant frequency among CAD patients (p = 0.034). CONCLUSIONS: High plasma concentrations of Hcy and low plasma levels of folate were associated with an increased risk of sCAD in the sample studied. We conclude that deficiencies in nutritional status may contribute to the relatively high incidence of CAD in Mexico.     

Alzheimer's disease in Brazilian elderly has a relation with homocysteine but not with MTHFR polymorphisms

OBJECTIVE: To investigate the association between total plasma homocysteine concentration, C677T and A1298C polymorphisms in MTHFR gene and Alzheimer's disease (AD) development. METHOD: Forty-three patients with probable (63%) and possible (37%) AD and 50 non-demented controls were evaluated. Groups did not differ as to gender, age, scholar years, diabetes, alcohol and coffee intake and physical activity. Total plasma homocysteine (Hcy) levels were determined by HPLC and genotyping for MTHFR by PCR/RFLP. Mann-Whitney "U" test was used to compare quantitative variable, Fisher-Freeman-Halton test to compare genotypes and allele proportions and Chi-square test to other qualitative variables. RESULTS: AD patients presented higher total plasma Hcy levels than controls and the difference was statistically significant. No differences in the C677T and A1298C MTHFR polymorphisms distributions were found between patients and controls. Plasma homocysteine concentration did not change with MTHFR genotypes. CONCLUSION: Our data confirms the association between increased plasma Hcy concentration and AD and suggests that neither C677T nor A1298C MTHFR polymorphisms contributed to genetic susceptibility for AD in elderly individuals in the Northeast of Brazil.     

Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 are vitamins that are necessary for remethylization of Hcy to methionine. The methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in remethylation of Hcy to methionine and supplies the required 5-methyltetrahydrofolate as the methyl donor for this reaction. It is well known that some antiepileptic drugs (AED) can lead to hyperhomocysteinemia by affecting the levels of folate and vitamin B-12. The C677T variant of MTHFR gene can also lead to hyperhomocysteinemia particularly when serum folate level is decreased. In this study, we investigated the levels of serum folate, vitamin B-12 and Hcy in epileptic patients receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy, and we also evaluated the probable contribution of the C677T variant of MTHFR gene in hyperhomocysteinemia. A total of 93 patients with idiopathic epilepsy receiving CBZ or VPA as monotherapy were included in this study. CBZ and VPA groups consisted of 29 and 64 patients, respectively. The control group comprised 62 healthy children. We measured serum folate, vitamin B-12 and Hcy levels in each group. We found that mean serum folate level was statistically lower and mean Hcy level was higher in epileptic patients receiving CBZ or VPA when compared with those of controls'. We also determined the C677T variants of MTHFR gene (as normal, heterozygote or homozygote) in epileptic patients. We compared the variant groups for serum folate, vitamin B-12 and Hcy levels and found no significant differences among them. In conclusion, C677T variants of MTHFR gene have no contribution in hyperhomocysteinemia in epileptic patients receiving CBZ or VPA.