MTHFRC677T基因多态性与胎儿神经管畸形关系

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)C677T位点基因多态性与胎儿神经管畸形的相关性。方法:分别选择52例既往孕有神经畸形胎儿的女性(观察组)和50例正常孕育史女性(对照组),取肘静脉血采用TaqMan探针SNP基因分型技术检测MTHFR C677T位点基因多态性,循环酶法检测血清同型半胱氨酸Hcy水平。分析MTHFR C677T位点基因多态性与血清Hcy水平以及胎儿神经管畸形易感的相关性。结果:观察组MTHFR C677T位点TT基因型、等位T基因频率高于对照组(P0.05)。观察组MTHFR C677T位点TT基因型受试者血清Hcy水平高于CC、CT基因型者(P0.05);对照组MTHFR C677T位点3种基因型之间差距没有统计学意义(P0.05)。二元logistic回归分析MTHFR C677T位点TT基因型[OR=2.003(95%CI:1.245～5.235)]携带者是胎儿神经管畸形易感的危险因素(P0.05)。结论:MTHFR C677T位点携带TT基因型人群血清Hcy水平偏高,是胎儿神经管畸形易感的高危人群。     

冠心病患者亚甲基四氢叶酸还原酶和内皮型一氧化氮合酶基因串联重复序列多态性与同型半胱氨酸水平相关性分析

目的 分析亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性、内皮型一氧化氮合酶(NOS3)的基因串联重复序列(VNTR)多态性与血浆同型半胱氨酸(Hcy)水平关系,以及2种突变对Hcy的影响。方法 选择冠心病患者153例,同时选取149例对照组。应用体外扩增-酶切长度多态性(PCR-RFLP)技术检测MTHFR基因C677T位点基因多态性、应用凝胶电泳检测NOS3 VNTR基因多态性。结果 Hcy水平在TT基因型中最高,在CC基因型中最低;冠心病(CHD)组的T等位基因频率显著高于对照组; CHD组的4a等位基因频率显著高于对照组。在CHD组中,Hcy水平在4a4a基因型中最高; TT4a4a基因型血浆Hcy最高,CC4b4b基因型血浆Hcy水平最低。结论 MTHFR C677T基因多态性和NOS3 VNTR可影响Hcy水平,其两者联合突变对血浆高Hcy有共同促进作用。     

体检人群血清同型半胱氨酸水平与MTHFRC677T基因型频率的调查

目的调查北京地区体检人群血清同型半胱氨酸(Hcy)水平及其代谢酶亚甲基四氢叶酸还原酶(MTHFR)基因的C677T基因型分布情况。方法利用全自动生化分析仪循环酶法检测892例体检者血清同型半胱氨酸水平,采用微测序法检测MTHFR C677T基因多态性,并进行基因分型。结果 TT基因型受检者血清Hcy水平高于CT基因型和CC基因型受检者水平,所调查的体检人群中男性血清Hcy水平显著高于女性,差异有统计学意义(P0.01)。结论MTHFR基因的C677T纯合突变型与血浆Hcy水平升高相关,此外健康人群血清Hcy水平存在年龄及性别差异。基因分型检测对于降低血清Hcy水平,预测脑卒中等心脑血管疾病具有重要意义。     

脑血管病患者5,10-亚甲基四氢叶酸还原酶基因C677T与同型半胱氨酸水平的相关性

目的探讨濮阳地区脑血管疾病(CVD)患者5,10-亚甲基四氢叶酸还原酶基因(MTHFR)677位点基因多态性分布,及与同型半胱氨酸(Hcy)水平的关系。方法采用基因芯片方法检测濮阳市人民医院和濮阳市中医院诊治的850例CVD患者MTHFR C677T基因多态性;酶循环法检测血清Hcy。结果 MTHFR基因CC纯合子在CVD疾病组的分布频率显著低于对照组(P0.001),TT纯合子在CVD疾病组的分布频率显著高于对照组(P0.001)。CVD疾病组血清Hcy浓度及高Hcy血症所占比例显著高于对照组,差异均有统计学意义(P0.001)。濮阳地区脑血管疾病患者MTHFRC677T基因型频率分别为:CC型26.11%、CT型41.18%,TT型32.71%;对应Hcy水平分别为(18.82±7.97)μmol/L、(19.93±7.35)μmol/L、(29.10±12.66)μmol/L;TT基因型患者血清Hcy水平明显高于CC基因型和CT基因型患者(P0.001)。不同年龄组间Hcy水平也存在差异,Hcy水平随着年龄增长而升高。结论 MTHFR基因突变可能与CVD的易感性密切相关;濮阳地区CVD患者中MTHFR基因多态性与Hcy水平明显相关,且不同年龄之间Hcy水平也存在明显差异。     

基于MTHFR基因多态性分析不同时期叶酸摄入与子痫前期及其亚型的相关性

目的基于亚甲基四氢叶酸还原酶(MTHFR)基因多态性分析不同时期叶酸(FA)摄入与子痫前期及亚型的相关性。方法选取2017年6月-2018年12月在该院进行治疗的180例子痫前期孕妇为研究组,根据不同子痫前期亚型将研究组分为轻度子痫前期组98例和重度子痫前期组82例;另选取同期该院收治的50例健康孕妇为对照组。比较各组孕妇血清中同型半胱氨酸(Hcy)、FA及维生素B_(12)(VitB_(12))含量,测定各组孕妇外周血中MTHFR基因多态性,比较不同基因型中Hcy、FA及VitB_(12)水平,并将各指标间及指标水平与病情程度进行相关性分析,同时观察各组孕妇妊娠结局。结果子痫前期孕妇血清中Hcy水平明显高于对照组,FA水平明显低于对照组,差异均有统计学意义(均P0.05)。轻度子痫前期孕妇血清中VitB_(12)水平明显低于对照组及重度子痫前期组,差异均有统计学意义(均P0.05)。子痫前期孕妇MTHFR基因C677T位点中CC及CT基因型比例明显低于对照组,子痫前期孕妇MTHFR基因C677T位点中TT基因型比例明显高于对照组;子痫前期孕妇T等位基因频率明显高于对照组,C等位基因频率明显低于对照组; TT及CT基因型孕妇血清中Hcy水平明显高于CC基因型孕妇,TT及CT基因型孕妇血清中FA及VitB_(12)水平明显低于CC基因型孕妇,差异均有统计学意义(均P0.05)。子痫前期孕妇血清中Hcy水平与FA呈负相关关系(P0.05);子痫前期孕妇血清中FA水平与VitB_(12)呈正相关关系(P0.05);血清中Hcy水与子痫前期孕妇病情程度呈正相关关系(P0.05);血清中FA水平与子痫前期孕妇病情程度呈负相关关系(P0.05)。重度子痫前期孕妇胎盘早剥、剖宫产、早产、低体质量儿、胎儿窘迫、新生儿窒息及死胎的发生率明显高于轻度子痫前期组及对照组,差异均有统计学意义(均P0.05)。结论 MTHFR基因C677T位点可通过影响体内Hcy、FA及VitB_(12)水平参与子痫前期过程,同时FA的缺乏可导致体内Hcy水平升高,可能是导致子痫前期发生重要原因,MTHFR基因多态性可作为预测子痫前期孕妇妊娠结局的风险指标。     

不良妊娠结局与夫妻MTHFR基因多态性的相关性及叶酸代谢风险评估策略的研究

目的 探讨夫妻亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase, MTHFR)基因C677T和A1298C多态性与不良妊娠结局的相关性及现有叶酸代谢风险等级评估策略的可行性。方法 选取145对曾有不良妊娠结局的夫妻和110对正常对照,应用Sanger测序检测MTHFR 677、1298位点多态性,分别比较病例组与对照组间女性、男性各基因型分布是否存在显著差异;据现有叶酸代谢风险等级评估策略对研究对象进行分级,比较两组中不同风险等级病例的分布是否存在显著差异。结果 病例组男性和女性MTHFR 677 位点C/C基因型频率均低于对照组,C/T、T/T基因型频率均高于对照组,两组中男性和女性的MTHFR 677位点3种基因型分布差异均有统计学意义（P＜0.05）;病例组男性和女性MTHFR 1298位点A/C基因型频率均高于对照组,A/A、C/C基因型频率均低于对照组,两组男性和女性MTHFR 1298位点3种基因型分布差异均无统计学意义（P＞0.05）;两组间男性和女性的叶酸代谢风险级别分布差异均有统计学意义（P＜0.05）。结论 女性MTHFR C677T多态性变异与不良妊娠结果有明显相关性,不能排除男性MTHFR C677T多态性改变与不良妊娠结局无关,建议孕前夫妻双方同时进行MTHFR基因多态性检测。可根据叶酸代谢风险分级策略,为夫妻双方制定合理的个体化叶酸增补方案。     

叶酸基因检测对于不明原因复发性自然流产的应用价值

目的探讨叶酸基因检测对于不明原因复发性自然流产的应用价值。方法选择2016年1月-2019年1月温州市中心医院截止不明原因复发性自然流产患者200例纳入研究,依据叶酸基因检测与否分为研究组、对照组,各100例。采用荧光定量PCR技术对叶酸MTHFR基因(C677T、A1298C)多态性实施检测,探究叶酸MTHFR基因型和不明原因复发性自然流产发生相对风险性。结果研究组血浆叶酸、红细胞叶酸表达水平均高于对照组(P0.05);研究组MTHFR基因C677T位点CC基因型频率高于对照组,但TT基因型频率低于对照组,(P0.05);两组MTHFR基因A1298C位点AA、AC、CC基因型的频率分布差异无统计学意义(P0.05);研究组MTHFR基因C677T位点C等位基因的频率高于对照组,但T等位基因频率低于对照组(P0.05);相较于MTHFR基因C677T位点CC纯合子,TT纯合子基因型患者出现不明原因复发性自然流产风险高3.29倍,OR值为3.288,95%CI为1.340～8.065。结论不明原因复发性自然流产患者体内叶酸水平降低,叶酸MTHFR C677T位点基因多态性和不明原因复发性自然流产发生存在相关性,且MTHFR基因C677T位点TT基因型可导致患病风险增加。     

孕期环境危险因素以及母亲MTHFR677C→T、血浆Hcy与儿童先天性心脏病的关系

目的:分析儿童不分型先天性心脏病(CHD)致病的危险因素,探讨CHD与母亲亚甲基四氢叶酸还原酶(MTHFR)677C→T和血浆同型半胱氨酸(Hcy)的相关性。方法:采用病例对照研究方法,分析80对CHD患儿与对照儿父母所处的环境因素并检测其MTHFR677位点的多态性和血浆Hcy的水平,进行单因素及多因素Logistic回归分析。并且通过母子配对,分析MTHFR677位点多态性和血浆Hcy水平与CHD发生的相互关联。结果:①母孕早期发烧(OR=4.465)、孕期居住乡村(OR=2.234)、孕期吸烟环境(OR=20.529)、母子血浆Hcy水平增高(OR=3.342,OR=3.069)为不分型CHD的危险因素。②儿童与母亲MTHFR677位点基因型之间没有明显的关联,双方血浆Hcy水平亦无明显关联(P均>0.05)。③病例组与对照组MTHFR677位点基因型差异无统计学意义(P>0.05),病例组母子血浆Hcy水平均显著高于对照组相应值(P均<0.01)。结论:①母孕早期发烧、孕期居住乡村、孕期吸烟环境、母子血浆Hcy水平增高为不分型CHD的危险因素。②MTHFR基因677C→T对血浆Hcy水平影响有待于进一步研究。③在CHD发生上,母子MTHFR基因677位点基因型之间和血浆Hcy水平之间均没有相关性。     

亚甲基四氢叶酸还原酶C677T基因多态性与2型糖尿病下肢血管病变

目的探讨亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)基因C677T多态性与2型糖尿病(T2DM)下肢血管病变的关系。方法选取344例T2DM患者和159名健康志愿者(对照组),其中T2DM患者分为两个亚组,糖尿病合并下肢血管病变组(DM+PAD组)176例和单纯糖尿病组(DM组)168例,检测3组同型半胱氨酸水平,采用PCR-芯片杂交技术检测亚甲基四氢叶酸还原酶C677T多态位点基因型,计算等位基因频率并统计分析。结果 DM+PAD组MTHFR基因纯合基因型(TT)、杂合基因型(CT)及T等位基因频率分别为11.4%、35.2%和29.0%,均明显高于DM组(分别为5.9%、27.4%和20.6%)和对照组(分别为3.1%、28.9%和17.6%),基因型和等位基因频率分布差异均有统计学意义(P0.05),而DM组和对照组之间的分布差异无统计学意义(P0.05)。单因素Logistic回归分析结果显示,MTHFR基因型C677T多态性与糖尿病下肢血管病变的发生密切相关(OR值及其95%CI分别为1.760、1.048~2.755)。携带T等位基因患者血中Hcy水平显著高于未携带T等位基因患者,差异有统计学意义(P0.01)。结论 MTHFR基因C677T多态性与北京地区2型糖尿病患者下肢血管病变相关,同型半胱氨酸的升高可能参与了下肢血管病变的发生与发展。     

奎文区成年人同型半胱氨酸水平及关键代谢酶基因多态性研究

目的调查潍坊市奎文区成年居民H型高血压检出比例、血浆同型半胱氨酸(Hcy)水平,探讨血浆同型半胱氨酸关键代谢酶亚甲基四氢叶酸还原酶(MTHFR C677T)基因多态性与H型高血压的关系,为制定有效的高血压防治措施提供科学依据。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLR)方法,对潍坊市奎文区740例成年人进行MTHFR C677T基因型分型和血浆Hcy水平检测。结果调查人群H型高血压检出比例为16.35%,男性高于女性,差异具有统计学意义(P0.05);所调查的人群Hcy水平为13.58±9.02,男性高于女性,差异具有统计学意义(P0.05);男性、女性MTHFR C677T基因TT、CT、CC基因频率分布,差异具有统计学意义(P0.05);H型高血压人群MTHFR C677T基因CC+CT和TT基因型频率与正常血压、非H型高血压人群比较,差异具有统计学意义(P0.05)。结论奎文区居民的H型高血压检出比例、血浆Hcy水平均偏高且存在性别差异,MTHFR C677T基因纯合突变可能是引起Hcy水平升高,进而引发H型高血压的重要遗传因素。     

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。     

妊高征患者亚甲基四氢叶酸还原酶基因多态的检测

目的　探讨妊高征患者亚甲基四氢叶酸还原酶 (MTHFR)基因C6 77T多态与血浆同型半胱氨酸 (Homo cysteine ,Hcy)、叶酸及维生素B12 水平的关系。方法　采用 (PCR -RFLPCPR -restrictionfragmentlengthpolymdor phism)法对 82例妊高征患者 (Hcy血症组和无Hcy血症组 )及 90例正常孕妇 (对照组 )进行MTHFR基因C6 77T等位基因检测 ,并同时测量孕妇血浆中的同型半胱氨酸、叶酸和维生素B12 水平。结果　妊高征组A(Hcy血症组 )纯合变异型T6 77/T6 77频率 (0 34)显著高于妊高征组B(无Hcy血症组 ) (0 11,P <0 0 1)和正常对照组 (0 13,P <0 0 1) ;各组中随 6 77T等位基因数量的增加 ,血浆Hcy水平也增加 ,但是对叶酸和维生素B12 水平没有明显影响。结论　MTH FR基因C6 77T多态可以导致妊高征孕妇血液中同型半胱氨水平升高 ,MTHFR基因C6 77T多态是妊高征发病的遗传危险因素之一     

MTHFR、MTRR基因多态性与多囊卵巢综合征的相关性研究

目的探讨亚甲四氢叶酸还原酶(MTHFR)、甲硫氨酸合成酶还原酶(MTRR)基因多态性与多囊卵巢综合征(PCOS)的相关性。方法应用病例对照研究,收集2018年4月-2018年8月在广东省妇幼保健院就诊的育龄期PCOS患者55例为PCOS组,选取46例月经规则、有排卵,并完成一次生育的非PCOS患者作为对照组。在PCOS组中,按HOMA稳态模型(HOMA-IR)分为两组,PCOS胰岛素抵抗(PCOS-IR)组和PCOS非胰岛素抵抗(PCOS-NIR)组,按多毛评分标准(m FG score)和血清游离雄激素指数(FAI)分为两组,高雄激素症组和非高雄激素症组,分别提取血浆,利用荧光定量PCR方法检测MTHFR基因C677T、A1298C及MTRR基因A66G的单核苷酸多态性(SNPs),同时采用化学发光法检测两组血浆维生素B12、叶酸及同型半胱氨酸(HCY)的含量。结果MTHFR基因C677T等位基因C在PCOS组分布频率高于对照组,差异有统计学意义(P<0.05),等位基因C使PCOS的风险增加2.077倍(95%CI:1.132~3.812)。677CC基因型在PCOS组的分布频率明显高于对照组,差异有统计学意义(P<0.05),野生基因型(CC)与纯合突变基因型(TT)相比,患PCOS的风险提高了4.392倍(95%CI:1.005~19.196)。两组MTHFR基因A1298C、MTRR基因A66G各基因型和等位基因频率的分布差异无统计学意义(P>0.05)。在PCOS组中,PCOS-IR组和PCOS-NIR组以及高雄激素症组和非高雄激素症组在MTHFR基因C677T、A1298C及MTRR基因A66G各基因型分布差异无统计学意义(P>0.05),MTHFR C677T、A1298C及MTRR A66G位点分布之间不存在交互作用(P>0.05)。PCOS组中HCY水平较对照组明显升高,差异有统计学意义(P<0.05),两组血清维生素B12、叶酸水平差异均无统计学意义(均P>0.05)。结论MTHFR基因C677T多态性与PCOS的发病有一定的相关性,CC基因型可增加PCOS的发生风险,但与胰岛素抵抗(IR)和高雄激素症的发生风险无关。MTHFR基因A1298C、MTRRA66G各基因型与PCOS的发生、IR及高雄激素症的发生无关,PCOS组HCY偏高。     

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.     

Interactions among polymorphisms in folate-metabolizing genes and serum total homocysteine concentrations in a healthy elderly population

BACKGROUND: Homocysteine concentrations are influenced by vitamin status and genetics, especially several polymorphisms in folate-metabolizing genes. OBJECTIVE: We examined the interactions and associations with serum total homocysteine (tHcy) and folate concentrations of polymorphisms in the following folate-metabolizing genes: methylenetetrahydrofolate reductase (MTHFR), reduced folate carrier 1 (RFC1), and glutamate carboxypeptidase II (GCPII). DESIGN: Healthy volunteers (436 men and 606 women; mean age: 77.9 y) were randomly selected from among residents of Oxford, United Kingdom. We determined the individual effects and interactions of the MTHFR 677C-->T, MTHFR 1298A-->C, RFC1 80G-->A, and GCPII 1561C-->T polymorphisms on serum tHcy and folate concentrations. RESULTS: Subjects with the MTHFR 677TT genotype had higher serum tHcy concentrations than did those with the MTHFR 677CC genotype (P < 0.001), and this effect was greater in subjects with low serum folate status (P for interaction = 0.026). The MTHFR 1298A-->C, RFC1 80G-->A, and GCPII 1561C-->T polymorphisms had no individual effects on serum tHcy or folate concentrations. There was no interactive effect of the MTHFR 677C-->T and MTHFR 1298A-->C polymorphisms on tHcy concentrations. An interaction (P = 0.05) was observed between the MTHFR 677TT and RFC1 80GG genotypes, whereby persons with this genotype combination had a mean (+/-SEM) serum tHcy concentration (18.5 +/- 1.2 micromol/L) that was 5.1 micromol/L greater than the mean value of 13.4 +/- 0.2 micromol/L for the whole population. CONCLUSIONS: Folate and tHcy concentrations were not affected individually by the MTHFR 1298A-->C, RFC1 80G-->A, or GCPII 1561C-->T polymorphisms or by combinations of the MTHFR 677C-->T and MTHFR 1298A-->C genotypes. An interaction between the MTHFR 677TT and RFC1 80GG genotypes was observed whereby persons with this combination had higher serum tHcy.     

Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women

OBJECTIVES: To examine the association between methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G gene polymorphisms and total homocysteine (tHcy), methylmalonic acid (MMA) and S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) levels; and to evaluate the potential interactions with folate or cobalamin (Cbl) status. SUBJECTS/METHODS: Two hundred seventy-five healthy women at labor who delivered full-term normal babies. Cbl, folate, tHcy, MMA, SAM and SAH were measured in serum specimens. The genotypes for polymorphisms were determined by PCR-restriction fragment length polymorphism (RFLP). RESULTS: Serum folate, MTHFR 677T allele and MTR 2756AA genotypes were the predictors of tHcy levels in pregnant women. Serum Cbl and creatinine were the predictors of SAM/SAH ratio and MMA levels, respectively. The gene polymorphisms were not determinants for MMA levels and SAM/SAH ratios. Low levels of serum folate were associated with elevated tHcy in pregnant women, independently of the gene polymorphisms. In pregnant women carrying MTHFR 677T allele, or MTHFR 1298AA or MTRR 66AA genotypes, lower Cbl levels were associated with higher levels of tHcy. Lower SAM/SAH ratio was found in MTHFR 677CC or MTRR A2756AA genotypes carriers when Cbl levels were lower than 142 pmol/l. CONCLUSIONS: Serum folate and MTHFR C677T and MTR A2576G gene polymorphisms were the determinants for tHcy levels. The interaction between low levels of serum Cbl and MTHFR (C677T or A1298C) or MTRR A66G gene polymorphisms was associated with increased tHcy.     

贵阳市育龄女性MTHFR和MTRR基因多态性与自然流产的相关性分析

目的分析贵阳市育龄女性亚甲基四氢叶酸还原酶(MTHFR)、甲硫氨酸合成酶还原酶(MTRR)基因多态性与自然流产的相关性,降低贵阳市育龄女性自然流产发生率。方法选取2016—2019年在贵阳市妇幼保健院进行孕前优生咨询的525例育龄女性为研究对象,按照有无自然流产史分为两组,病例组175例女性,对照组350例女性。比较两组育龄女性MTHFR C677T、A1298C及MTRR A66G基因型和等位基因分布。结果病例组MTHFR C677T野生基因型CC型69例(39.4%),杂合突变CT型76例(43.4%),纯合突变TT型30例(17.1%),对照组MTHFR C677T野生基因型CC型154例(44.0%),杂合突变CT型164例(46.9%),纯合突变TT型32例(9.1%),两组比较差异具有统计学意义(χ²=7.20,P<0.05);病例组的T等位基因频率为38.9%,较对照组T等位基因频率(32.6%)明显升高,差异有统计学意义(χ²=4.07,P<0.05)。两组MTHFR A1298C基因型分布比较差异无统计学意义(P...     

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.     

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.     

Folate status and a new repletion cut-off value in a group of healthy Majorcan women

BACKGROUND AND AIMS: Folate status is complex, complicated to assess and we lack consensus for laboratory determination.Total plasma homocysteine (Hcy) is a sensitive marker of folate status. The aim of this study was choosing a plasma total homocysteine (tHcy) measurement method and folate repletion level; assess the mutation C677T frequency for methylenetetrahydrofolate reductase (MTHFR) and the prevalence of hyperhomocysteinemia in healthy Majorcan women. METHODS: The measurement methods were compared using 219 women. Folate status assessment was determined by plasma tHcy, serum and erythrocyte folate and C677T for MTHFR in 342 healthy women. The mutation frequency is established with 146 of them.RESULTS: The measurement method comparison is summarized by Y = 1.013 (IC 95% 0.959, 1.069) X +0.829 (IC 95% 0.485, 1.170). The folate repletion level was set at Hcy < or = 8.6 micromol/l. Women (67.1%) are heterozygotic and do not carry the mutation. Homozygotic frequency is 18.5%, significantly higher in women under 40 years (P = 0.033). Hyperhomocysteinemia prevalence is 19.3%, and 51.7% in the younger group. CONCLUSIONS: Hcy determination by polarized fluorescence immunoassay reflects folate status. Levels < or = 8.6 micromol/l suggest folate repletion, which is less frequent in homozygotes. Population frequency for homozygotic-TT alleles for C677T-MTHFR reductase and hyperhomocysteinemia is significantly higher in women under 40 years.