血浆同型半胱氨酸水平及MTHFR基因多态性与阿尔茨海默病的关系

目的 探讨血浆同型半胱氨酸(Hcy)水平及MTHFR基因多态性与阿尔茨海默病(AD)的关系. 方法 选取43例AD患者(AD组),应用高效液相色谱-电化学检测(HPLC-ED)法测定血浆Hcy水平,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测MTHFR基因多态性,同时测定血浆叶酸、维生素B12水平,并与40例健康老年人(对照组)比较. 结果 AD组血浆Hcy水平为(25.43±5.60)μmol/L,显著高于对照组的(9.81±2.86)μmol/L(P＜0.01),血浆叶酸、维生素B12水平明显低于对照组(P＜0.05);MTHFR基因型有3种,即纯合子(T/T)型、杂合子(T/C)型和纯合子(C/C)型,两组MTHFR基因型和等位基因频率比较差异均无统计学意义(P＞0.05). 结论 高Hcy血症是AD发生和发展的一个重要危险因素.     

MTHFR基因C677T位点多态性与胎儿生长受限的相关性

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T位点多态性与胎儿生长受限(FGR)的关系。方法:FGR患者62例,正常妊娠妇女65例。聚合酶链反应—限制性内切酶片段长度多肽性(PCR-RFLP)法检测MTHFR C677T基因多态性;荧光偏振免疫法测定血浆总同型半胱氨酸水平;微粒子酶免分析法测定血浆叶酸、VitB12浓度。结果:①FGR组MTHFR C677TC/T基因型频率显著高于正常对照组,C/C基因型频率显著低于对照组,总的突变T等位基因频率显著高于对照组(P<0.05)。②FGR组MTHFRT/T基因型Hcy水平较C/C、C/T基因型患者显著增高,而血清叶酸水平则明显降低(P<0.05)。血清VitB12水平在FGR3种基因型之间差异无显著性(P>0.05)。对照组MTHFR C677T3种基因型之间血清Hcy、叶酸、VitB12,水平差异无显著性(P>0.05)。结论:MTHFR基因C677T位点多态性与FGR有关,高同型半胱氨酸血症是FGR发病的危险因素。     

叶酸、同型半胱氨酸及MTHFR C677T基因多态性与肾功能的关系

同型半胱氨酸是蛋氨酸代谢生成的一种含硫氨基酸,也是反应性血管损伤氨基酸,代谢紊乱可形成高同型半胱氨酸血症。叶酸又名维生素B9,是人体必需的一种微量营养素,缺乏可导致高同型半胱氨酸水平。亚甲基四氢叶酸还原酶(MTHFR)是叶酸和同型半胱氨酸代谢途径中的一个关键酶,MTHFR 677 C-T的突变致酶的活性和耐热性下降导致同型半胱氨酸升高,高同型半胱氨酸血症可引起血栓性疾病和动脉粥样硬化,近年来发现这也是影响肾功能的一个新的独立危险因素。本文对叶酸、血浆Hcy水平和MTHFR C677T基因多态性与肾功能损伤关系进行概述。     

孕妇血浆叶酸、维生素B12和同型半胱氨酸水平测定及临床意义

目的 通过测定孕妇血浆叶酸、VitB12和同型半胱氨酸水平,了解其与发生妊娠期并发症的关系.方法 对2004年3月～2005年6月在产科门诊及住院妊娠中、晚期孕妇以及健康育龄妇女,测定血浆叶酸、VitB12 400例,同时测血浆Hcy 165例,采用酶免疫检测法检测同型半胱氨酸浓度;叶酸及Vit B12测量采用放射免疫法.结果 ①正常非孕妇女、孕12～27+6周、28～36+6周、37～42周及产后的孕妇血浆FA、Vit Bi2及Hcy含量比较,差异无统计学意义(P＞0.05);②孕妇并发妊高征、贫血、心肌缺血或损害及胎儿异常者与正常晚孕组及正常非孕组血FA、Vit B12及Hcy异常水平比较差异有统计学意义(P＜0.05,0.01).结论 孕妇妊娠期缺乏叶酸及Vit B12,将可能发生高同型半胱氨酸血症,从而对母儿造成危害.     

上海地区孕妇MTHFR C677T基因多态性与血浆同型半胱氨酸水平的关联性分析

目的 了解上海市孕妇MTHFR基因型的分布情况,分析MTHFR C677T基因多态性与高同型半胱氨酸血症的关联性,为高危孕妇的遗传筛查及围产期叶酸摄入的个性化提供依据。方法 选取上海市五所社区医院2015年1月~2015年6月门诊建卡孕妇1000例,随访了解基本信息、孕期危险因素暴露及叶酸摄入情况,以基因芯片法检测MTHFR基因型,循环酶法检测血浆同型半胱氨酸。结果 上海地区孕妇MTHFR C677T基因CC型、CT型、TT型的检出频率分别为33.0%、49.2%、17.8%,等位基因C、T的频率为57.6%、42.4%,样本人群处于H-W平衡状态。血浆同型半胱氨酸浓度为11.22（9.15,13.52）μmol/L,其中911例（91.6%）正常,84例（8.4%）属轻度高同型半胱氨酸血症。经多因素logistic回归分析,CT型与TT型发生高同型半胱氨酸血症的OR值分别为2.18（95%CI:1.11~4.25）和6.26（95%CI:3.13~12.53）。结论 MTHFR基因C677T多态性与孕妇血浆同型半胱氨酸水平存在关联,携带等位基因T者可视为高危孕妇,孕期叶酸补充可适量增加。     

孕妇血浆叶酸、维生素B12和同型半胱氨酸水平测定及临床意义

目的:通过测定孕妇血浆叶酸、VitB12和同型半胱氨酸水平,了解其与发生妊娠期并发症的关系。方法:对2004年3月～2005年6月在产科门诊及住院妊娠中、晚期孕妇以及健康育龄妇女,测定血浆叶酸、VitB12400例,同时测血浆Hcy165例,采用酶免疫检测法检测同型半胱氨酸浓度;叶酸及VitB12测量采用放射免疫法。结果:①正常非孕妇女、孕12～27 6周、28～36 6周、37～42周及产后的孕妇血浆FA、VitB12及Hcy含量比较,差异无统计学意义(P>0.05);②孕妇并发妊高征、贫血、心肌缺血或损害及胎儿异常者与正常晚孕组及正常非孕组血FA、VitB12及Hcy异常水平比较差异有统计学意义(P<0.05,0.01)。结论:孕妇妊娠期缺乏叶酸及VitB12,将可能发生高同型半胱氨酸血症,从而对母儿造成危害。     

妊高征患者同型半胱氨酸代谢酶基因多态性研究

目的:检测妊高征患者同型半胱氨酸代谢酶N5,10-亚甲基四氢叶酸还原酶(MTHFR)及胱硫醚-β-合成酶(CBS)基因多态性,分析其与妊高征发病的关系,解析遗传因素在该病中的作用地位。方法:孕产妇均抽取空腹外周静脉血4 ml,分离血清,采用循环酶法小分子捕获技术测定同型半胱氨酸浓度,叶酸及Vit B12测量采用发光免疫法,全血提取DNA用于PCR检测MTHFR C677T、PCR扩增及程序采用等位基因特异性扩增(ASA)技术检测CBS G919A和CBSC572T基因型。统计软件分析数据。结果:本次实验发现妊娠高血压患者与正常对照间的MTHFR C677T位点和CBSC572T位点突变频率差别有统计学意义,而CBS G919A位点则无差别。同时发现,两组间的Hcy和叶酸浓度有明显差别,而Vit B浓度差别不明显。结论:妊娠高血压的可能同时是由于遗传因素和叶酸缺乏造成的。     

荆州地区同型半胱氨酸及其代谢酶基因多态性与不良孕产史之间的关系

目的 探讨亚甲基四氢叶酸还原酶(5,10-Methylenetetrahydrofolate reductase,MTHFR)和甲硫氨酸合成酶还原酶(Methionine synthase reductase,MTRR)基因多态性及血浆同型半胱氨酸(Homocysteine,Hcy)水平与不良孕产史之间的关系。方法 采用病例对照研究方法,收集有不良孕产史的孕妇100名做为病例组,同时选取无不良孕产史的孕妇100名做为对照组。采用Taqman-MGB技术检测口腔黏膜上皮细胞MTHFR基因C677T,A1298C和MTRR基因A66G位点基因多态性;循环酶法测定血浆Hcy浓度。结果 200名孕妇中,MTHFR基因C677T位点T等位基因频率分布为41. 5%,A1298C位点C等位基因频率为20. 8%,MTRR基因A66G位点G等位基因频率为27. 5%。两组人群相比,MTHFR基因C677T,A1298C和MTRR基因A66G位点基因多态性分布差异无统计学意义(P0. 05)。200名孕妇血浆Hcy平均水平为(5. 09±1. 72)μmol/L,不同基因型孕妇血浆Hcy水平差异无统计学意义(P0. 05)。与对照组相比(4. 76±1. 71)μmol/L,病例组(5. 43±1. 67)μmol/L血浆Hcy水平显著升高,且差异具有统计学意义(P 0. 05)。Logistic回归分析显示,孕妇血浆Hcy水平每升高一个单位,不良孕产发生的风险增加0. 27倍(OR=1. 27,95%CI:1. 07～1. 52,P 0. 05);同样以血浆Hcy水平中位数5. 23μmol/L为界值,经Logistic回归分析显示,血浆Hcy水平较高的孕妇不良孕产发生风险是Hcy水平较低孕妇的1. 25倍(OR=2. 25,95%CI:1. 28～3. 96,P 0. 05)。结论 荆州地区孕妇Hcy代谢相关酶基因MTHFRC677T、A1298C和MTRRA66G位点基因多态性与不良孕产史无明显关联,但血浆Hcy水平升高是不良妊娠发生的重要危险因素。     

兰州地区育龄妇女叶酸代谢与早产的相关性研究

目的探讨兰州地区育龄妇女血清同型半胱氨酸(Hcy)水平、5,10-亚甲基四氢叶酸还原酶(MTHFR)及甲硫氨酸合成酶还原酶(MTRR)基因多态性与早产的相关性。方法选取2015年2月-2016年7月在甘肃省妇幼保健院产检并分娩的孕妇1 298例为研究对象,按照新生儿是否早产,将新生儿及其母亲分为早产组和足月组,应用RT-PCR技术检测MTHFR基因C677T、A1298C和MTRR A66G位点的多态性,同时应用循环酶法检测血浆Hcy水平。比较早产组和足月组间各种基因型与血清Hcy水平的差异及相关性。结果早产组血浆Hcy水平明显高于足月组,差异均有统计学意义(P0. 05)。高Hcy为早产的危险因素(OR=2. 672,P=0. 032)。血浆Hcy水平在MTHFR C677T、A1298C和MTRR A66G突变纯合子患者中显著高于突变杂合子和野生型患者,且野生型患者血浆Hcy水平最低,差异均有统计学意义(均P0. 05)。结论早产孕妇血浆Hcy水平明显高于足月孕妇,孕妇血浆Hcy水平与早产相关,补充叶酸前需检测叶酸代谢关键基因的SNP类型,以便更有效的补充叶酸,从而降低早产的发生率。     

血液透析病人血浆总同型半胱氨酸水平及其影响因素

目的　为探讨国内血液透析病人血浆总同型半胱氨酸 (tHCY)水平及其影响因素 ,以及与N2 ,N10-亚甲基四氢叶酸还原酶 (MTHFR)基因的关系。方法　分别采用高效液相 (HPLC)法和聚合酶链反应 -限制性片段长多态性 (PCR -RFLP)法检测血液透析病人在透析前后血浆tHCY水平和MTHFR基因型 ,及血液透析的相关指标。结果　血液透析病人血浆tHCY水平为 (32 0± 8 5) μmol/L ,明显高于正常对照组 (P <0 0 1) ;血液透析对tHCY的清除率为 (19 8± 6 2 ) % ;MTHFR基因第 6 77位点C/C正常纯合者占 75% (12 / 16 ) ,C/T杂合突变者占 2 5% (4/ 16 ) ,未发现T/T纯合突变者 ;C/T杂合突变组血浆tHCY水平为 (34 3± 4 2 ) μmol/L ,C/C正常纯合组为 (2 8 4± 5 8) μmol/L ,两组比较差异无显著性 ;血浆tHCY水平与血浆白蛋白水平呈正相关 (r =0 6 0 )。结论　本研究结果提示血液透析病人血浆tHCY水平升高 ,血液透析对同型半胱氨酸有一定的清除作用。血液透析病人MTHFR基因C6 77T突变与高同型半胱氨酸血症的关系有待进一步证实     

Dietary and genetic determinants of homocysteine levels among Mexican women of reproductive age

OBJECTIVE: To evaluate the independent and joint effects of dietary folate, vitamin B(12) consumption and methylenetetrahydrofolate reductase (MTHFR) polymorphisms (677C>T and 1298A>C) on the circulating folate and homocysteine (Hcy) levels among Mexican women of reproductive age. DESIGN: A cross-sectional, population-based study. SUBJECTS: The first 130 healthy non-pregnant women (aged 16-34 years) who agreed to participate in a reproductive cohort in Morelos, Mexico. MAIN OUTCOME MEASUREMENTS: Dietary intakes of vitamin B(12) and folate were estimated using a semiquantitative food frequency questionnaire. MTHFR 677C>T and 1298A>C polymorphisms were ascertained using the PCR-based method. Serum levels of Hcy and folate were determined using high-performance liquid chromatography and radioimmunoassay, respectively. RESULTS: Genotype frequencies for the MTHFR 677C>T polymorphism were 21.5% (CC), 52.3% (CT) and 26.2% (TT) among Mexican women. Of the population, 22% had the MTHFR 1298AC genotype, while no individual carried the 1298CC genotype. We observed an increased level of Hcy among carriers of the 677TT genotype, compared to carriers of the 677CC genotype. The highest level of Hcy was observed among MTHFR 677TT carriers with low B(12) intake (<2.0 microg/day), which resulted with a significant interaction (P=0.01). CONCLUSION: Vitamin B(12) is an important determinant of Hcy levels in Mexico. Supplementation of folic acid with vitamin B(12) may be preferable when the MTHFR 677T variant allele is prevalent.     

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

OBJECTIVE: The purpose of this study was to investigate the effect of the interaction between the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes and serum levels of B vitamins on serum homocysteine levels in pregnant women. DESIGN: A cross-sectional study. SETTING: Ewha Womans University Hospital, Seoul, Korea. SUBJECTS: A total of 177 normal pregnant women, 24.6+/-1.1 weeks of gestation, in a 6-month period during 2001-2002. INTERVENTIONS: Serum vitamin B2, vitamin B6, and homocysteine analyses were conducted using high-performance liquid chromatography methods. Serum folate and vitamin B12 concentrations were determined using a radioimmunoassay kit. MTHFR gene mutation was investigated by the polymerase chain reaction of a genomic DNA fragment. RESULTS: Serum homocysteine was higher in women with the T/T genotype than those with the C/T or C/C genotype of the MTHFR gene (P<0.05). Serum homocysteine was negatively correlated with serum folate in all MTHFR genotypes (P<0.001), and the correlation between the two serum levels was the strongest in the T/T genotype. Serum homocysteine was higher in the subjects with the T/T MTHFR genotype only when the serum folate was below the median level. Explanatory power of B vitamin status as predictors of serum homocysteine levels was more pronounced in the T/T genotypes (68.5%) compared with the C/T (37.9%) or C/C genotypes (20.6%). CONCLUSIONS: Serum homocysteine levels in pregnant women varied significantly with MTHFR genotype and the serum B vitamin status. Higher serum folate, vitamin B2, and vitamin B12 concentrations may lessen the MTHFR genotypic effect on serum homocysteine levels.     

B-group vitamins, MTHFR C677T polymorphism and carotid intima-media thickness in clinically healthy subjects

OBJECTIVE: Plasma B-group vitamins and age may affect the carotid intima-media thickness (IMT) in subjects with different 677TT genotype of the methylenetetrahydrofolate reductase (MTHFR) gene. DESIGN: A hospital-based cross-study. SETTING: Genomic and Vascular Center, Changhua Christian Hospital, Changhua, Taiwan. SUBJECTS: Five hundred and forty-one clinically healthy subjects. INTERVENTION: Fasting plasma, homocysteine (Hcy), vitamin B(6), vitamin B(12), folate and B-mode carotid ultrasound. RESULTS: MTHFR genotype, plasma concentrations of folate, vitamin B(6) and vitamin B(12) and age were significantly correlated to the plasma Hcy concentration. MTHFR 677TT carriers had higher concentrations of Hcy than did subjects with the CC and CT genotypes. Age, sex, body mass index and plasma Hcy were independent contributors to increase carotid IMT. However, with stratification by mean value of age and B-group vitamins concentrations, we found that at advanced age, lower plasma folate and vitamin B(12) were three risk factors involved in the enhancing effect of the MTHFR 677TT genotype on the increase of plasma Hcy and carotid IMT. CONCLUSION: MTHFR 677TT-related carotid atherosclerosis was only identified in healthy elderly subjects with lower level of plasma folate and vitamin B(12). SPONSORSHIP: Changhua Christian Hospital.     

Vitamin B-12 status is inversely associated with plasma homocysteine in young women with C677T and/or A1298C methylenetetrahydrofolate reductase polymorphisms

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms may negatively influence one-carbon metabolism and increase health risks in women of reproductive age. The effect of MTHFR single nucleotide polymorphisms at bp 677 and/or 1298 and differences in folate and vitamin B-12 status on plasma homocysteine concentration in women of reproductive age (20-30 y; n = 186) were investigated. From the multivariate regression model, homozygotes (n = 23) for the C677T MTHFR variant had plasma homocysteine concentrations that were higher (P < 0.05) than those observed in the other 5 genotype groups, including those who were heterozygous for both variants (677CT/1298AC; n = 32). Plasma homocysteine was negatively associated with plasma vitamin B-12 concentration (P = 0.015) and serum folate (P = 0.049), with the degree of correlation between plasma vitamin B-12 and homocysteine concentrations dependent on MTHFR genotype. The C677T and A1298C MTHFR polymorphisms were significant predictors (P < 0.05) of plasma homocysteine when regression analysis was used to model plasma homocysteine concentration as a function of genotype, supplement use, serum folate and plasma vitamin B-12 concentration. Plasma homocysteine decreased as vitamin B-12 concentration increased (P = 0.0005) in individuals who were heterozygous for both the C677T and A1298C variants with nonsignificant trends (P = 0.114-0.128) in individuals homozygous for either the C677T or A1298C variants. In contrast, within the group of individuals with the wild-type genotype for both the C677T and A1298C MTHFR variants, homocysteine was not associated with changes in plasma vitamin B-12 concentrations. These data suggest that enhancing vitamin B-12 status may significantly decrease homocysteine in young women with C677T and/or A1298C MTHFR polymorphisms, even when vitamin B-12 concentrations are within the normal range.     

2型糖尿病合并冠心病患者的同型半胱氨酸水平及代谢关键酶基因多态性特点

目的探讨中国北方地区糖尿病合并冠心病者同型半胱氨酸(Hcy)及其代谢相关酶亚甲基四氢叶酸还原酶(MTHFR)C677T及胱硫醚β-合成酶(CBS)844 ins 68基因多态性的特点。方法研究对象均为北方汉族人群,包括无血缘关系的70名糖尿病合并冠心病患者、71名糖尿病患者和85名健康人群。应用荧光偏振免疫法(FPIA)测定Hcy水平,应用微粒子酶免分析免疫法(MEIA)测定血浆叶酸、维生素B12浓度,同时测定血脂。应用聚合酶链反应分析MTHFR C677T与CBS844 ins 68基因多态性。结果糖尿病合并冠心病组(DM+CHD组)Hcy中位数为14.8μmol/L,显著高于DM组(11.1μmol/L)和对照组(11.2μmol/L),(P<0.01),DM组与对照组之间差异无显著性(P>0.05)。DM+CHD组的T等位基因频率(45%)明显高于糖尿病组(26.8%)和对照组(31.2%),(P<0.01)。三组CBS844 ins 68的基因型及等位基因频率差异无显著性(P>0.05)。本研究定义Hcy>15μmol/L为高Hcy血症(HHcy)。Logistic回归分析显示HHcy的OR值为4.547(95%CI1.970～10.496),(P<0.01);MTHFR677携带T基因的OR值为2.369(95%CI1.160～4.841),(P=0.018);CBS844 ins 68基因的OR值为0.384(95%CI0.033～4.423),(P=0.443)。结论HHcy、MTHFR677携带T基因可能是中国北方地区汉族人2型糖尿病合并冠心病发生的危险因素。     

Methionine synthase reductase 66A->G polymorphism is associated with increased plasma homocysteine concentration when combined with the homozygous methylenetetrahydrofolate reductase 677C->T variant

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are important for homocysteine remethylation. This study was designed to determine the influence of genetic variants (MTHFR 677C-->T, MTHFR 1298A-->C, and MTRR 66A-->G), folate, and vitamin B-12 status on plasma homocysteine in women (20-30 y; n = 362). Plasma homocysteine was inversely (P < 0.0001) associated with serum folate and plasma vitamin B-12 regardless of genotype. Plasma homocysteine was higher (P < 0.05) for women with the MTHFR 677 TT/1298 AA genotype combination compared with the CC/AA, CC/AC, and CT/AA genotypes. Women with the MTHFR 677 TT/MTRR 66 AG genotype had higher (P < 0.05) plasma homocysteine than all other genotype combinations except the TT/AA and TT/GG genotypes. There were 5.4-, 4.3-, and 3.8-fold increases (P < 0.001) in risk for plasma homocysteine in the top 5, 10, and 20%, respectively, of the homocysteine distribution for subjects with the MTHFR 677 TT compared with the CC and CT genotypes. Predicted plasma homocysteine was inversely associated with serum folate (P = 0.003) and plasma vitamin B-12 (P = 0.002), with the degree of correlation dependent on MTHFR 677C-->T genotype. These data suggest that coexistence of the MTHFR 677 TT genotype with the MTRR 66A-->G polymorphism may exacerbate the effect of the MTHFR variant alone. The potential negative effect of combined polymorphisms of the MTHFR and MTRR genes on plasma homocysteine in at-risk population groups with low folate and/or vitamin B-12 status, such as women of reproductive potential, deserves further investigation.     

The plasma homocysteine, folic acid and vitamin B12 levels in young people with high risk for cardiovascular disease and its relation to metylentetrahydrofolate reductase (MTHFR) gene polymorphism

INTRODUCTION: Hyperhomocysteinemia is an independent risk factor for cardiovascular morbidity. AIM: The study was designed to evaluate the total homocysteine level and MTHFR C677T polymorphism frequency of 122, healthy, young adults who had increased risk for cardiovascular disease. The serum levels of folic acid and vitamin B12 were also measured. METHODS: Immunoassay, PCR-RFLP methods were used. The statistical analysis was performed by SPSS program. RESULTS: The frequency of the gene-polymorphism was not different significantly in the study group compared to a Hungarian neonatal sample: although in the increased risk group the frequency of homozygous 677TT polymorphism was higher (14.8%), and heterozygosity was smaller (41%). There was no association between MTHFR gene polymorphism and homocysteine levels. A significant negative correlation was found between the folic acid and homocysteine, and between the vitamin B12 and homocysteine levels correlating with the literature. The mean serum total homocysteine level of the group without vitamin supplementation (n: 86) was 9.8 +/- 3.3 micromol/l, while in the other group with vitamin uptake (n: 36) this level was 7.5 +/- 3.0 micromol/l. There was a significant difference between the homocysteine levels of men and women. CONCLUSION: The results of the study correlate with the literature. It would be useful to call the attention of the Hungarian population to the importance of vitamin supply.     

B-vitamins, homocysteine metabolism and CVD

The present review focuses on the B-vitamins, i.e. folate, vitamin B12, vitamin B6 and riboflavin, that are involved in homocysteine metabolism. Homocysteine is a S-containing amino acid and its plasma concentrations can be raised by various constitutive, genetic and lifestyle factors, by inadequate nutrient status and as a result of systemic disease and various drugs. Hyperhomocysteinaemia is a modest independent predictor of CVD and stroke, but causality and the precise pathophysiological mechanism(s) of homocysteine action remain unproven. The predominant nutritional cause of raised plasma homocysteine in most healthy populations is folate insufficiency. Vitamin B12 and, to a lesser extent, vitamin B6 are also effective at lowering plasma homocysteine, especially after homocysteine lowering by folic acid in those individuals presenting with raised plasma homocysteine. However, riboflavin supplementation appears to be effective at lowering plasma homocysteine only in those individuals homozygous for the T allele of the C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. This gene codes for the MTHFR enzyme that produces methyltetrahydrofolate, which, in turn, is a substrate for the remethylation of homocysteine by the vitamin B12-dependent enzyme methionine synthase. Individuals with the MTHFR 677TT genotype are genetically predisposed to elevated plasma homocysteine, and in most populations have a markedly higher risk of CVD.     

Physiologic changes in homocysteine metabolism in pregnancy: a longitudinal study in Spain

Objective

The aim was to investigate whether pregnancy-induced changes in total homocysteine (tHcy) are associated with folate and vitamin B12 nutritional status, genetic C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) enzyme, and gestation outcome at a time when folic acid supplementation started to be recommended in the Spanish health system.

Methods

In total 154 pregnant women were recruited from among gynecologic patients of the Alcorcón Public Hospital Outpatient Clinic (Madrid, Spain). Blood tests were performed at weeks 15, 24, and 32 of pregnancy. Total Hcy, folate, and vitamin B12 serum fasting concentrations were measured using an IMx system. Genotype analyses were done by polymerase chain reaction/restriction fragment/length polymorphism analysis.

Results

Folate and vitamin B12 serum concentrations decreased significantly (P < 0.01) through pregnancy and reached the lowest values in the third trimester. Serum tHcy concentrations were significantly (P < 0.01) lower in the second trimester but increased in the third trimester. Frequencies of MTHFR C667T genotype were CC (35.7%), CT (57.2%), and TT (7.1%). Total Hcy concentration was not statistically influenced by maternal genotype. Plasma folate was the single negative predictor of maternal tHcy in the first trimester of pregnancy; 11.1% of gestations resulted in intrauterine growth restriction, 7.9% in gestational diabetes mellitus, and 4.8% in gestational hypertension. No significant differences in serum folate, vitamin B12, or tHcy concentrations were found in complicated pregnancies and these were unrelated to MTHFR genotype.

Conclusion

Although tHcy seems to be physiologically low in this Spanish population and unrelated to folate and B12 nutritional status, C677T MTHFR genotype, and some pregnancy complications, we support the statement that appropriate folate concentration may be important throughout pregnancy to prevent abnormalities associated with altered status (e.g., neural tube defects). According to our study, supplementation with folic acid seems to achieve this purpose because diet alone may be insufficient. In addition, a poor vitamin B12 status, as measured by plasma levels, may indicate that supplementation of both vitamins is needed.     

High plasma homocysteine is associated with the risk of coronary artery disease independent of methylenetetrahydrofolate reductase 677C-->T genotypes

Hyperhomocysteinemia is an independent risk factor for coronary artery disease (CAD). The aim of this study was to investigate the relations between the methylenetetrafolate reductase (MTHFR) 677C-->T genotypes, B-vitamins (folate, vitamin B-12 and B-6), homocysteine and the risk of CAD. In this case-control study, patients who were identified by cardiac catheterization as having at least 50% stenosis of one major coronary artery were assigned to the case group (n=121). Healthy individuals with normal blood biochemical values were assigned to the control group (n=155). Healthy subjects were matched to case subjects for age. The concentrations of plasma homocysteine, serum folate, vitamin B-12, plasma pyridoxal 5'- phosphate (PLP) and MTHFR 677C-->T gene polymorphism were obtained. The T-allele carriers had significantly higher plasma homocysteine concentration compared to subjects with the 677CC genotype. The MTHFR 677C-->T genotypes were associated with plasma homocysteine after adjusting for various potential risk factors in the case and pooled groups. The MTHFR genotypes were found to have no associations with the risk of CAD. However, plasma homocysteine (>or= 12.5 micromol/L) (OR, 3.49; 95% CI, 1.23-9.88) had a significant association with increased risk of CAD even after additionally adjusted folate status. High plasma homocysteine concentration had a direct effect on the risk of CAD independent of MTHFR 677C-->T genotypes.