ASSOCIATION OF PLASMA HOMOCYSTEINE LEVEL AND N^5, N^(10) -METHYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISM WITH CEREBRAL INFARCTION

Objective. To investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level.Methods. The plasma Hcy level was measured by capillary electrophoresis- ultraviolet detection and the gene polymorphism of N5, N10 - methylenetetrahydrofolate reductase (MTHFR) was studied with PCR - RFLP assay in 43 patients with cortical cerebral infarction and 42 healthy controls.Results. The plasma Hcy level of the patients ( 19. 3 + 6. 0 μ mol/L) was markedly higher than that of the controls (13.7 + 5.4 μ mol/L) ( t = 4. 16, P ＜ 0. 001). There are 3 genotypes, C/C, C/T and T/T, about base - variation of MTHFR gene at locus 677. The plasma Hcy level of the subjects with T/T genotype was higher than that of subjects with other genotypes. However, the frequencies of each genotype and allele were not significantly different between the patients and the controls.Conclusions. The elevated plasma Hcy level is a risk factor for atherothrombotic cerebral infarction, and is related to the C→T mutation at locus 677 of MTHFR gene.

Interaction between maternal 5,10-methylenetetrahydrofolate reductase C677T and methionine synthase A2756G gene variants to increase the risk of fetal neural tube defects in a Shanxi Han population

Background The 5,10-methylenetetrahydrofolate reductase （MTHFR） and methionine synthase （MS） are attractive candidates for screening for risk of neural tube defects （NTDs）. The aim of the current study was to investigate maternal MTHFR and MS polymorphisms and the interaction between them and their influence on children with NTDs in the Shanxi Province of northern China. Methods Fifty-one mothers who previously had children with NTDs constituted the case group and 51 age-matched mothers with children that were unaffected by any birth defects constituted the control group. All subjects were genotyped for MTHFR C677T and MS A2756G polymorphisms. SPSS 11.5 software package was used for all analyses. Results There was a significant difference for MTHFR genotype distribution for one site （C677T） between the case and control groups. The T allele frequencies were significantly higher in the case group than in the control group （55.9% vs. 35.3%, P 〈0.05）. A lack of association was observed for the MS A2756G polymorphism. There was an interaction between the maternal MTHFR C677T genotype and MS A2756G genotype. Conclusion Genetic interaction between MTHFR and MS genes raises the probability of neural tube defects.

RELATIONSHIP OF HOMOCYSTEINE AND GENE POLYMORPHISMS OF ITS RELATED METABOLIC ENZYMES WITH ALZHEIMER'S DISEASE

Objective To investigate the relationship of plasma homocysteine (Hcy) levels and the gene polymorphisms of N5, N10-methylenetetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CBS) with Alzheimer’s disease (AD). Methods Plasma Hcy levels were measured by means of high voltage capillary electrophoresis with ultra-violet detection, the polymorphisms of C677T in exon 4 of MTHFR gene and 844ins68 in exon 8 of CBS gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 105 AD patients and 102 non-AD controls. All controls were excluded from cardiocerebrovascular disorders and other diseases. Results The plasma Hcy level in AD patients (16.04 ± 3.84 μmol/L) was significantly higher than that in the controls(11.94 ± 3.87 μmol/L, P < 0.001). There were no significant differences of the genotype and allele frequencies of MTHFR C677T mutation and CBS 844ins68 mutation between the patients and controls. However, the T allele of MTHFR gene was found to relate with the plasma Hcy level increase in all subjects. Conclusion The elevated plasma Hcy level in AD patients is probably involved in the pathogenesis of AD, which may be due to the environmental factor rather than genetic factors of the mutations of MTHFR and CBS.

血浆Hcy水平及MTHFR基因多态性与脑梗死的关系

目的 探讨血浆同型半胱氨酸 ( homocysteine,Hcy)水平与脑血管病间联系及血浆 Hcy水平升高的遗传性因素。方法 对 4 3例皮质脑梗死患者及 4 2名健康对照者采用毛细管电泳 -紫外检测法测定血浆 Hcy水平、PCR-RFL P技术分析 N5 ,N10 -亚甲基四氢叶酸还原酶 ( N5 ,N10 -methylenetetrahydrofolate reductase,MTHFR)基因多态性。结果 脑梗死患者血浆 Hcy水平 ( 1 9.3± 6.0 μmol/ L)显著高于对照者 ( 1 3 .7± 5.4 μmol/ L) ( t=4 .1 6,P<0 .0 0 1 ) ;MTHFR基因 677位点碱基变异致 3种基因型 :C/ C、C/ T和 T/ T,血浆 Hcy水平 T/ T基因型者最高 ,C/ T基因者居中 ;但患者组与对照组间各基因型及等位基因频率无显著性差异。结论 血浆 Hcy水平升高是动脉粥样硬化性脑梗死的危险因素 ,与 MTHFR基因 677位点碱基 C→ T突变有关。

血浆Hcy水平及MTHFR基因C667T突变与肝硬化的相关性研究

目的探讨血浆同型半胱氨酸(Hcy)水平与肝硬化的关系及血浆Hcy水平升高的遗传因素。方法采用高效液相色谱法(HPLC)测定64例肝硬化患者、42例非肝硬化肝病患者和60名健康对照者血浆Hcy水平,聚合酶链反应限制性片段长度多态性技术(PCR RFLP)分析N5,N10亚甲基四氢叶酸还原酶(MTHFR)基因C667T突变。结果肝硬化组血浆Hcy水平[(14.6±6.9)μmol/L]显著高于非肝硬化肝病组[(9.3±5.2)μmol/L]和正常对照组[(7.1±3.9)μmol/L](均P<0.01);MTHFR基因677位点碱基变异致3种基因型C/C、C/T和T/T,肝硬化组3种基因型分布频率(18.8%,50.0%,31.2%)明显高于非肝硬化肝病组(45.2%,40.5%,14.3%)和正常对照组(53.3%,33.4%,13.3%)(均P<0.01),非肝硬化肝病组3种基因型分布频率与正常对照组比较,差异无显著性意义(均P>0.05);血浆Hcy水平增高与T/T基因型别相关。结论血浆Hcy水平升高是肝硬化的一个危险因素,可能与MTHFR基因677位点碱基C→T突变有关。

EB病毒转化的永生性人B淋巴母细胞中MTHFR基因的表达

为检测用 EB病毒转化建立的永生性人 B淋巴母细胞株中 N5 ,N1 0 -亚甲基四氢叶酸还原酶(MTHFR)基因的表达及其 c DNA序列 ,用 EB病毒转化人外周血 B淋巴细胞 ,建立永生性细胞株后 ,从培养细胞中提取总 RNA,用 RT- PCR法扩增 MTHFR基因 c DNA的不同片段 ,进行 PAGE电泳分析和 c DNA序列测定。结果显示永生性人 B淋巴母细胞中有 MTHFR基因表达 ,其 c DNA序列与文献报道的人肝脏MTHFR基因 c

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 N^2，N^(10)-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。