遗忘性轻度认知功能障碍与MTHFR C677T基因多态性及血浆同型半胱氨酸水平研究

目的探讨MTHFR C677T基因多态性及血浆同型半胱氨酸(homocysteine,Hcy)水平与遗忘型MCI(amnestic MCI,a MCI)的关系。方法选入50例a MCI患者(a MCI组)和60例健康老年人(对照组)为研究对象,记录并比较2组年龄、性别、高血压、糖尿病、吸烟、嗜酒。测定并比较2组胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、尿酸(uric acid,UA)、血浆Hcy浓度及MTHFR C677T基因多态性分布。采用蒙特利尔认知评估量表(montreal cognitive assessment,MoCA)评价aMCI患者认知功能与MTHFR C677T基因多态性和血浆Hcy水平的关系。采用Logistic回归分析a MCI发生的独立危险因素。结果 2组研究对象在年龄、性别构成、受教育年限、高血压、糖尿病、高血脂、吸烟和饮酒等一般资料方面比较差异无统计学意义(P>0.05)。2组研究对象的TG、HDL-C水平比较,差异无统计学意义(P>0.05);2组在TC、LDL-C、UA、Hcy水平及MTHFR C677T基因型分布和等位基因频率比较,差异具有统计学意义(P<0.05)。a MCI组TC、Hcy水平显著高于对照组(P<0.05)。与对照组比较,a MCI组TT基因型增高,CC基因型降低,T等位基因频率增高,C等位基因降低,差异有统计学意义(P<0.05)。不同MTHFR C677T基因型a MCI组Hcy水平显著高于对照组,差异均具有统计学意义(P<0.05)。2组TT基因型血浆Hcy水平均显著高于CC基因型(P<0.05)。CC、CT和TT基因型aMCI患者对应的平均MoCA评分分别为(24.37±1.21)分、(23.26±1.02)分和(22.14±0.96)分,差异具有统计学意义(P<0.05),两两比较差异也具有统计学意义(P<0.05)。多元Logistic回归分析显示,UA与a MCI存在负相关关系,TC、Hcy和MTHFR C677T基因型与aMCI存在正相关关系。结论 MTHFR C677T基因突变致血浆Hcy浓度升高可能是aMCI发病及不断进展的重要危险因素。     

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。     

如皋市H型高血压患者MTHFR C677T基因多态性与同型半胱氨酸水平分析

目的探讨H型高血压患者的亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与血清同型半胱氨酸(Hcy)水平。方法对H型高血压患者进行MTHFR C677T基因分型检测,并对各基因型患者高Hcy水平进行统计分析。结果 310例H型高血压患者中MTHFR C677T基因CC型、CT型、TT型分别占22.90%(71例)、45.48%(141例)、31.62%(98例)。CC型患者Hcy水平为(20.82±8.83)μmol/L,CT型患者为(20.99±13.14)μmol/L,TT型患者为(25.17±13.01)μmol/L。TT型患者血清Hcy水平高于CC型和CT型患者(P值均0.05),且TT型男性患者Hcy水平高于女性(P0.05)。结论 H型高血压患者中TT型患者Hcy水平较高,对高血压患者进行MTHFR C677T基因检测,对降低心脑血管病的发病率有着十分重要的意义。     

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.     

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。     

MTHFR C677T、CBS 844ins68基因多态性与潍坊市城乡居民H型高血压的关系

目的探讨亚甲基四氢叶酸还原酶MTHFR C677T、胱硫醚-β-合成酶CBS 844ins68基因多态性与潍坊市城区、农村居民H型高血压的关系,以进一步了解H型高血压发病的遗传学机制。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLR),对潍坊市城区740名和农村800名成年人(包括高血压患者),进行MTHFR C677T、CBS 844ins68基因型分型和血浆同型半胱氨酸(Hcy)水平检测。结果所调查的人群高同型半胱氨酸血症患者城区、农村分别占55.81%、35.63%,城区高Hcy(10μmol/L)者413人(55.81%),农村285人(35.63%),城区高于农村(P0.01);城区H型高血压患病率(25.27%)高于农村(11.75%)(P0.01);城区组MTHFR C677T基因TT、CT、CC基因频率分别为41.62%、47.16%、11.22%,农村组为25.88%、58.75%、15.38%,差异有统计学意义(P0.01);高血压人群中,MTHFR C677T基因TT基因型的Hcy水平(15.17±5.37μmol/L)高于CC+CT基因型(9.71±5.81μmol/L),(P0.01),TT基因型H型高血压患者的比例(71.81%)高于CC+CT基因型(38.68%)(P0.01);CBS 844ins68DD、DI基因型在城市、农村间人群基因型和等位基因频率分布、高血压人群Hcy水平及H型高血压患者比例,差异无统计学意义(P0.05)。结论潍坊市居民的MTHFR C677T基因型频率、Hcy水平、H型高血压患病率存在城乡差异,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,CBS 844ins68基因多态性与H型高血压无明显相关。     

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。     

贵州省清镇市围孕期女性血清同型半胱氨酸水平及影响因素分析

目的了解贵州省清镇市围孕期女性血清同型半胱氨酸(homocysteine,Hcy)水平及影响因素。方法选择2019年3-6月在清镇市妇幼保健院就诊的健康围孕期女性1421人,根据知情同意原则,采用循环酶法检测血清Hcy浓度,采用荧光定量PCR法检测5,10-亚甲基四氢叶酸还原酶(MTHFR) C677T基因位点多态性。结果①30岁和≥30岁年龄组的Hcy水平分别为(6.20±2.30)、(5.94±2.13)μmol/L,差异有统计学意义(P 0.05)。②孕前、早孕期、中孕期、晚孕期、产后的血清Hcy水平分别为(7.14±1.56)、(6.17±2.19)、(5.72±2.28)、(6.93±2.93)、(7.10±2.39)μmol/L,差异有统计学意义(P 0.05)。③根据MTHFR C677T基因位点多态性,CC、CT、TT基因型女性的围孕期血清Hcy水平分别为(7.23±2.19)、(7.60±2.20)、(9.02±2.53)μmol/L,差异有统计学意义(P 0.05)。结论围孕期女性血清Hcy水平与年龄、围孕期不同阶段以及MTHFR C677T基因多态性有关,监测Hcy水平对围孕期保健有重要的指导意义。     

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。     

高原世居藏族血浆同型半胱氨酸与相关基因

目的了解高原世居藏族血浆同型半胱氨酸(Hcy)水平与5,10-亚甲基四氢叶酸还原酶(MTHFR)及甲硫氨酸合成还原酶(MTRR)基因多态性。方法于2017年6—7月,采用单纯随机抽样方法,在西藏自治区拉萨市城关区(海拔3 650 m)抽取447名30～70岁的藏族居民;检测血浆Hcy水平、MTHFR C677T、MTRR A66G位点基因多态性,应用SPSS 17.0软件处理数据。结果血浆Hcy水平为15.40(13.40,17.90)μmol/L,除在61～70岁年龄组性别没有统计学差异外,男性的Hcy水平[16.55(14.40,19.68)]均高于女性[15.00(12.90,16.90)](P 0.05);H型高血压的患病率为13.9%(62/447),检出率为60.2%(62/103);血浆Hcy水平在MTHFR C677T TT型最高,组间具有统计学差异(P 0.05);影响H型高血压的因素是年龄、收缩压、性别和MTHFR C677T(P 0.05)。结论高原世居藏族男性、 60岁女性、TT型人群是健康管理的重点。     

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.     

Plasma homocysteine concentrations in Greek children are influenced by an interaction between the methylenetetrahydrofolate reductase C677T genotype and folate status

Risk factors established at young ages may set the stage for later cardiovascular disease (CVD). Elevated total homocysteine (tHcy) in blood is an emerging risk factor for CVD, yet few studies have been conducted in children, especially in the Mediterranean. We described plasma tHcy concentrations in a group of healthy Greek children and examined its relation with physiologic, metabolic, and genetic variables. Fasting blood samples were collected from 186 students, 11.6 +/- 0.4 years old, and tHcy, folate, vitamin B-12, and routine biochemistry variables in plasma were measured. The methylenetetrahydrolate reductase (MTHFR) C677T genotype was determined and anthropometric and dietary data were obtained. The distribution of tHcy was positively skewed with a median of 7.9 micromol/L (mean: 8.2 +/- 2.3 micromol/L; range: 4.4-22.2 micromol/L). tHcy was inversely related to plasma folate (r = -0.34, P < 0.0001), vitamin B-12 (r = -0.20, P = 0.008), and glucose (r = -0.15, P = 0.045). An interaction between the MTHFR genotype and plasma folate on tHcy was detected (P = 0.047). Specifically, the homozygous mutant TT genotype was associated with higher tHcy only in children with lower plasma folate (< 19.9 nmol/L), (P = 0.012). In our sample of healthy Greek children, plasma tHcy concentrations were higher than values reported in children of Northern European descent and were associated with folate, vitamin B-12, and glucose in plasma. The results also show that, similar to adults, plasma folate concentration is important in determining the contribution of the MTHFR C677T mutation to tHcy concentrations in children.     

Frequency of hyperhomocysteinemia in hemodialysis patients with folic acid supplementation

BACKGROUND: It is known that hyperhomocystinemia is an independent risk factor for development of atherosclerosis. In end stage renal disease the frequency of hyperhomocystinemia is much greater than in normal populations. AIM: In this study homocystein (Hcy), folic acid and vitamin B12 concentrations were determined in 125 chronic renal failure patients being on folic acid supplementation (3 mg/day). In 107 patients the frequency of C667T polymorphism of methylene tetrahyrofolate reductase (MTHFR) was also determined. The relationships between these parameters were also studied. RESULTS: It was found that in these patients who are under continuous folic acid supplementation the mean level of homocysteine was 16.8 +/- 7.2 mumol/L, a value considerably lower than the homocysteine concentration reported for non-supplemented patients. The elevation of homocysteine concentrations was independent of gender, time spent in renal replacement therapy, and the type of renal replacement therapy (hemodialysis: 17.6 +/- 12.6; hemodiafiltration: 16.6 +/- 12.9 mumol/L). Data showed an inverse relation between plasma homocysteine concentrations and the concentrations of folic acid and vitamin B12. Moderately severe hyperhomocystinemia (Hcy > 20 mumol/L) was found in about 30% of patients. In those the frequency of patients for homozygous T677 allele of MTHFR was about 25-30%. However, in all ESRD patients the frequency of the homozygotes was the same then in the normal population. Homocysteine plasma levels correlated with MTHFR polymorphism: in the wild type group Hcy was 14 +/- 7 mumol/L, in the heterozygous group was 17.2 +/- 6.2 mumol/L, and in the homozygous group was 21 +/- 19 mumol/L. CONCLUSIONS: Long-term folic acid supplementation decreased the homocysteine level in end stage renal disease patients. However, in folic acid resistant group, who were in 30% homozygotes for C667T of MTHFR (suggesting that homocysteine-methionine remethylation cycle is disturbed), instead of the administration of folic acid, methylene tetrahydrofolate supplementation might be considered.     

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.     

A common mutation A1298C in human methylenetetrahydrofolate reductase gene: association with plasma total homocysteine and folate concentrations.

Methylenetetrahydrofolate reductase (MTHFR) is one of the main regulatory enzymes of homocysteine metabolism. Previous studies revealed that a common mutation in MTHFR gene C677T is related to hyperhomocysteinemia and occlusive vascular pathology. In the current study, we determined the prevalence of a newly described mutation in the human MTHFR gene A1298C, and the already known C677T mutation, and related them to plasma total homocysteine and folate concentrations. We studied 377 Jewish subjects, including 190 men and 186 women aged 56.8 +/- 13 y (range 32-95 y). The frequency of the homozygotes for the A1298C and the C677T MTHFR mutations was common in the Jewish Israeli population (0.34 and 0.37, respectively). Subjects homozygous (TT) for the C677T mutation had significantly greater plasma total homocysteine concentrations (P < 0.01) than subjects without the mutation (CC). Homozygotes (CC) for the A1298C mutation did not have elevated plasma total homocysteine concentrations. Our study indicated that subjects with the 677CC/1298CC genotype had significantly lower concentrations (P < 0. 05) than those with a 677CC/1298AA genotype. Neither mutation (the A1298C and the C677T) was associated with established cardiovascular risk factors such as hypertension, elevated total cholesterol or body mass index.     

Folate intake at RDA levels is inadequate for Mexican American men with the methylenetetrahydrofolate reductase 677TT genotype

Since the establishment of the 1998 folate recommended dietary allowance (RDA), the methylenetetrahydrofolate reductase (MTHFR) 677C-->T variant has emerged as a strong modifier of folate status. This controlled feeding study investigated the adequacy of the RDA, 400 microg/d as dietary folate equivalents (DFE), for Mexican American men with the MTHFR 677CC or TT genotype. Because of the interdependency between folate and choline, the influence of choline intake on folate status was also assessed. Mexican American men (n = 60; 18-55 y) with the MTHFR 677CC (n = 31) or TT (n = 29) genotype consumed 438 microg DFE/d and total choline intakes of 300, 550 (choline adequate intake), 1100, or 2200 mg/d for 12 wk. Folate status response was assessed via serum folate (SF), RBC folate, plasma total homocysteine (tHcy), and urinary folate. SF decreased (P < 0.001) 66% to 7.9 +/- 0.7 nmol/L (means +/- SEM) in men with the 677TT genotype and 62% to 11.3 +/- 0.9 nmol/L in the 677CC genotype. Plasma tHcy increased (P < 0.0001) 170% to 31 +/- 3 micromol/L in men with the 677TT genotype and 18% to 11.6 +/- 0.3 micromol/L in the 677CC genotype. At the end of the study, 34% (677TT) and 16% (677CC) had SF concentrations <6.8 nmol/L and 79% (677TT) and 7% (677CC) had tHcy concentrations >14 micromol/L. Choline intake did not influence the response of the measured variables. These data showed that the folate RDA is not adequate for men of Mexican descent, particularly for those with the MTHFR 677TT genotype, and demonstrated a lack of influence of choline intake on the folate status variables measured in this study.     

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。     

Association between C677T/MTHFR genotype and homocysteine concentration in a Kazakh population

We recently suggested that due to insufficient intake of vegetables, low folate status and mild homocysteinemia might exist in the Kazakh population. To clarify the determinants of homocysteine concentrations among this population, we determined concentrations of serum folate, albumin, creatinine, vitamin B12, and the C677T/ MTHFR genotype in 110 Kazakh individuals and compared these with plasma total homocysteine. In Kazakh, after adjustment for age and sex, folate was correlated with plasma total homocysteine, whereas concentrations in those with the TT genotype was almost twice as high as in those with the CC and CT genotypes (19.7+/-1.8 micromol/L vs. 10.7+/-0.5 micromol/L, p<0.001). Our results suggest that the C677T/MTHFR genotype is associated with homocysteine concentrations in this population and this association might be affected by other factors, such as folate status.