妊娠早期MTHFR C677T基因多态性与同型半胱氨酸的相关分析

目的:分析妊娠早期妇女5,10-亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性及其与同型半胱氨酸的关联性。方法:选取2015年6月—2016年7月来温州市中医院行孕早期检查的妊娠妇女1052例,采用荧光探针PCR技术检测MTHFR C677T位点基因型,循环酶法检测同型半胱氨酸。结果:1052例妊娠早期妇女中CC基因型443例(42.1%),CT基因型469例(44.6%),TT基因型140 (13.3%);等位基因C、T的频率分别64.4%(1355例)、35.6%(749例)。本地区基因型频率与多数地区有差异,具有本地区特征性。CC、CT、TT基因型个体的血同型半胱氨酸浓度分别为(5.8±1.5)μmol/L、(5.7±1.2)μmol/L、(6.4±2.7)μmol/L,TT基因型个体的血同型半胱氨酸浓度高于CC基因型和CT基因型个体。结论:MTHFR C677T基因多态性与同型半胱氨酸的浓度有关,TT基因型妊娠妇女,从孕早期开始密切关注血同型半胱氨酸浓度,加强叶酸补充。     

双亲5,10-亚甲基四氢叶酸还原酶基因多态性与子代神经管畸形易感性的关系

目的 定量评价双亲5,10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与子代神经管畸形(NTDs)发生的关联性及关联强度,为利用双亲MTHFR 677位点基因型预测和评价子代NTDs的发病风险提供依据.方法 制定原始文献的纳入和排除标准及检索策略.检索中外数据库,收集有关亲代MTHFR基因C677T多态性与NTDs相关性的研究报告,按照MTHFR基因677位点基因型分类,分别整理子代患NTDs的双亲基因型频数数据,应用RevMan5.0软件对各文献进行异质性检验和Meta分析,得出合并后的OR值及其95%CI.结果 共33篇文献符合纳入标准.数据合并结果显示,母亲MTHFR基因677位点TT/CC、CT/CC基因型频率与子代NTDs易感性之间有统计学意义,OR值(95%CI)分别为1.68(1.32～2.14)、1.20(1.07～1.35);父亲MTHFR基因677位点TT/CC、CT/CC基因型频率与子代NTDs易感性有统计学意义,OR值(95%CI)分别为1.38(1.08～1.76)、1.32(1.13～1.55).结论 双亲MTHFR基因C677T多态性均是子代NTDs发病的重要危险因素.

Abstract：

Objective To explore the relationship between 5, 10-methylenetrahydrofolate reeducates gene polymorphism of the parents and the susceptibility to their offspring having neural tube defects. To forecast and evaluate the onset risk of neural tube defects (NTDs) on the basis of 5, 10-methylenetrahydrofolate reeducates (MTHFR) C677T polymorphism on parents of the patients.Methods Electronic search strategy was carried out among the five databases from home and abroad to collect qualified research papers, according to the inclusion and exclusion criteria. Case-control studies on association between MTHFR polymorphism and susceptibility to NTDs were collected and divided into two groups as mothers and fathers. The combined OR values and their 95% CI were calculated with Review Manager 5.0. Results 33 eligible studies were included. Statistics of the combined data showed a significant difference between the mothers with NTDs offspring carrying TT/CC, CT/CC of MTHFR gene C677T and controls. The pooled OR (95%CI) were 1.68 (1.32-2.14)and 1.20 (1.07-1.35) respectively. These was a significant difference between the fathers of the offspring with NTDs that carrying of TT/CC, CT/CC of MTHFR gene C677T and controls. The pooled ORs (95%CI) were 1.38 (1.08-1.76) and 1.32 (1.13-1.55) respectively. Conclusion The results suggested that the paternal and maternal MTHFR gene C677T polymorphism were risk factors to NTDs.     

儿童5,10-亚甲基四氢叶酸还原酶C677T多态性与神经管畸形易感性关系的研究

目的采用Meta分析的方法,探索5,10-亚甲基四氢叶酸还原酶(MTHFR)和神经管畸形(NTDs)之间的关系。方法在中国知网和Pubmed等国内外数据库中,根据检索标准,收集儿童MTHFR C677T多态性与NTDs相关的文献,应用Stata 11.0软件对各文献进行数据分析。结果共9篇文献符合纳入标准。分析后发现,在TT/CC、CT+TT/CC和TT/CT+TT遗传模式下,OR值分别为1.78(95%CI1.12,2.81)、1.28(95%CI1.07,1.55)和1.73(95%CI 1.07,2.78)。结论 MTHFRC677T多态性与NTDs之间存在显著关联。儿童MTHFR基因C677T多态性是神经管畸形发病的一个危险因素。     

5,10-亚甲基四氢叶酸还原酶C677T基因多态性与不明原因复发性流产相关性的Meta分析

目的:评价5,10-亚甲基四氢叶酸还原酶(MTHFR)C667T基因多态性与不明原因复发性流产(URSA)的相关性。方法:在PubMed数据库、中国知网数据库(CNKI)、万方数据库、中国生物医学文献数据库(CBM)和维普中文期刊全文(VIP)数据库中全面检索关于MTHFR C667T基因多态性与URSA相关的文献,按照既定的筛选标准进行筛选,对纳入的文献进行质量评价,并采用RevMan5.3软件进行meta分析。结果:共有31篇文献被纳入本次的meta分析,累计病例组3706人,对照组3937人。meta分析结果显示MTHFR C677T基因多态性与URSA的发生呈相关性T/C:OR=1.41,95%CI 1.23~1.61,P0.05;CT/CC:OR=1.23,95%CI 1.03~1.47,P0.05;(TT+CT)/CC:OR=1.45,95%CI 1.21~1.74,P0.05;TT/CC:OR=1.98,95%CI 1.51~2.59,P0.05)。病例组与对照组有统计学差异(P0.05)。在亚组分析中发现,国内人群中基因型为TT的女性发生URSA的风险较基因型为CC的女性高3.56倍,基因型TT和等位基因T是URSA的遗传性风险因素TT/CC:OR=3.56,95%CI 2.71~4.69,P0.05;T/C:OR=1.88,95%CI 1.66~2.13,P0.05;CT/CC:OR=1.67,95%CI 1.36~2.04,P0.05;(TT+CT)/CC:OR=2.07,95%CI 1.71~2.50,P0.05,病例组与对照组的差异均有统计学意义(P0.05),但在国外人群中,包括亚洲其他国家人群中,各基因型分布URSA病例组与正常对照组差异并无统计学意义(P0.05)。结论:MTHFR C667T基因多态性与URSA呈相关性,在中国人群中MTHFR C667T基因多态性是URSA的遗传性高风险因素,但在国外人群中包括亚洲其他国家中并未显示相关性,仍有待加大样本进一步论证。     

四氢叶酸还原酶基因多态性与中国妇女先兆流产关系meta分析

目的:探讨亚甲基四氢叶酸还原酶基因多态性与中国妇女先兆流产的关系。方法:检索万方、中国知网和Pubmed等中英文数据库,截止时间至2020年8月10日。经筛选最终纳入7篇文献。采用State软件进行数据分析,计算95%可信度区间和比值比评估两者关系并行异质性检测和发表偏倚评估。结果:MTHFR(C677T)基因T与C OR=1.13,95%CI 1.06～1.20,Ph=0.902;TT与CC OR=1.19,95%CI 1.05～1.35,Ph=0.379;TT与(CC+CT)OR=1.19,95%CI 1.06～1.34,Ph=0.955。提示MTHFR(C677T)基因多态性与中国妇女先兆流产存在明显相关性。而MTHFR(A1298C)基因5种遗传模型在两组间差异均无统计学意义。结论:MTHFR(C677T)基因多态性可能增加中国妇女先兆流产的风险,而MTHFR(A1298C)基因多态性可能与中国妇女先兆流产不存在相关性。     

孕期化学物接触及基因多态性与先天性心脏病

目的 探讨5,10-亚甲基四氢叶酸还原酶MTHFR基因C677T多态性和孕期接触化学物与先天性心脏病的关系.方法 采用病例-对照研究设计,选择144例病例和168例对照,采用面访法和聚合酶链反应-限制性片段长度多态性分析法(PCR-RFLP)进行检测,运用多因素Logistic回归模型分析MTHFR基因C677T多态性与孕期化学物接触对先心病的作用强度和交互作用.结果 MTHFR677TT基因型发生先天性心脏病的风险是MTHFR677CT或CC基因型的3.215倍(95%CI=1.958～5.280);孕期化学物接触与子代先天性心脏病关联强度OR值为2.150(95%CI=1.041～4.442);MTHFR677TT基因型与孕期化学物接触具有正相加交互作用,交互作用的效应量(RERI)、归因交互效应百分比[AP(AB)]和纯因子间归因交互效应百分比[AP*(AB)]分别为4.938,60.23%,68.59%.结论 MTHFR基因C677T变异可与孕期接触化学物协同增加子代罹患先心病的危险性.     

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。     

MTHFR基因多态性与中国男性不育关系的meta分析

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与中国男性不育的关系。方法:通过检索中英文数据库,截止时间至2020年12月18日,经筛选最终纳入19篇文献。采用State软件计算OR和95%可信度区间,并进行异质性、敏感性分析和发表偏倚的评估。结果:5种遗传模型T比C (OR=1.51, 95%CI1.34～1.71)、TC比CC(OR=1.13, 95%CI 1.09～1.18)、TT比CC(OR=2.18, 95%CI 1.72～2.76)、TT比(CC+CT)(OR=1.81, 95%CI 1.51～2.17)和(TT+CT)比CC(OR=1.57, 95%CI 1.34～1.84),MTHFR(C677T)基因多态性与中国男性不育存在明显相关性。结论:MTHFR(C677T)基因多态性可能增加中国男性不育的风险。     

5,10-亚甲基四氢叶酸还原酶C677T基因多态性与急性淋巴细胞白血病易感性 关系的Meta分析

目的 运用Meta分析的方法综合评价5,10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与急性淋巴细胞白血病(ALL)的相关性.方法 制定原始文献的纳入和排除标准及检索策略.检索中外文数据库,收集有关MTHFR基因C677T多态性与ALL相关性的研究报告,采用TT/CC+CT以及TT/CC基因型比较模型进行定量综合分析,然后按年龄(儿童或成年人)分亚组进行分析.结果 综合分析显示,MTHFR基因677位点TT/CC+ CT、TT/CC模型计算OR值(95％CI)分别为0.87(0.69～1.09)、0.82(0.63～ 1.06);在儿童组TT/CC+ CT、TT/CC模型计算OR值(95％CI)分别为0.92(0.79～1.08)、0.88(0.75～1.05),在成年人组TT/CC+CT、TT/CC模型计算OR值(95％CI)分别为0.45(0.26 ～0.77)、0.41(0.22～0.72).结论 MTHFR基因C677T突变与儿童ALL无关联,但可能减弱成年人ALL发生的危险.     

亚甲基四氢叶酸还原酶C677T基因多态性与食管癌易感性关系的Meta分析

[目的]评价亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与食管癌易感性的关系。[方法]检索CNKI、Pubmed、ScienceDirect、Springer Link等数据库,获得有关MTHFRC677T基因多态性与食管癌易感性的关系的文献,剔除不符合要求的文献,然后应用Meta分析软件RevMan4.3对各研究原始数据进行统计处理,计算合并OR值及95%可信区间。[结果]按照纳入标准,共纳入系统评价的文献共有10个病例对照研究组,其中食管癌患者2162例,对照3114例,CT和TT基因型同CC基因型比较,OR值分别为1.47(95%CI:1.10～1.96)和1.60(95%CI:1.07～2.39),Z值分别为2.62和2.30,对应的P值分别为0.009和0.02。[结论]对目前相关研究结果的Meta分析显示,MTHFRC677T基因多态性与食管癌易感性之间存在相关,即携带MTHFR C677T杂合基因型(CT)及突变纯合基因型(TT)的个体发生食管癌的危险性较高。     

降钙素受体基因多态性与广州地区绝经后妇女骨密度关系研究

目的探讨降钙素受体基因多态性与绝经后妇女人群骨密度相互关系。方法选取年龄≥42岁的广州地区汉族绝经后妇女(自然绝经≥2年)231例,采用双能X线吸收法(DEXA)测定其全身、腰椎2~4(L2~4)、股骨颈(neck)、粗隆间(inter)、Ward’三角和大转子(troch)区等部位的骨密度(BMD)值,并采用聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术检测外周血白细胞基因组降钙素基因多态性。结果231例受试对象中,CTR基因型分别为CC型194例(占84.0%),CT型33例(占14.3%),TT型4例(占1.7%),基因型分布符合Hardy-weinberg定律。分析三种基因型与骨密度的关系显示,它们各自所代表的骨密度值之间差异并无统计学意义。结论降钙素基因C1377T多态性不能作为预测广州地区汉族绝经后妇女发生骨质疏松危险性的遗传标志。     

MTHFRC677T基因多态性与复发性流产的关系

目的探讨亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase，简称MTHFR）C677T基因多态性与复发性流产（recurrent abortion，简称RA）发病的相关性。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析RA组60例和对照组60例MTHFRC677T的基因型。结果RA孕妇及胚胎绒毛组织MTHFR677TT基因型频率和T等位基因频率高于对照组（p〈0．05）；MTHFR677的3种基因型在流产组和对照组的分布差异有统计学意义（p〈0．01），流产组CT＋TT基因型频率也高于对照组（p〈0．05）。结论RA患者和胚胎绒毛组织MTHFR677TT突变与RA有相关性。     

孕期疾病与5,10-亚甲基四氢叶酸还原酶基因对先天性心脏病影响的病例-对照研究

目的探讨5,10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性、孕期疾病及其交互作用与子代先天性心脏病的关系。方法采用以医院为基础的病例对照研究设计,按照纳入和剔除标准选择144例先天性心脏病(先心病)病例与168例健康对照,通过聚合酶链反应-限制性片段长度多态性(polymerase chain reaction restricted fragment length polymorphism,PCR-RFLP)检测MTHFR C677T基因型,并对母亲孕期患病情况进行调查;采用单因素和多因素非条件logistic回归模型,分析影响因素关联强度及交互作用。结果病例组和对照组MTHFR 677TT基因型频率和T等位基因频率的差异有统计学意义(χ2=22.38,P<0.001;χ2=20.36,P<0.0001),MTHFR 677TT基因型与先心病风险的OR值为3.215(95%CI:1.958～5.280);妊高症、孕期感冒发烧是先心病的危险因素,其OR值分别为4.545(95%CI:1.788～11.553)、3.885(95%CI:1.756～8.592);MTHFR 677TT基因型与孕期两种疾病之间具有正相加交互作用,调整混杂因素前后,TT基因型与妊高症的I(AB)为5.469、6.011,AP(AB)为32.33%、33.67%,AP*(AB)为36.28%、37.54%;与孕期感冒发烧之间的I(AB)为4.165、5.951,AP(AB)为30.02%、31.36%,AP*(AB)为31.65%、33.38%。结论 MTHFR 677TT基因型是先心病的易感因素;妊高症、孕期感冒发烧是子代先心病发生的危险因素;MTHFR 677TT基因型与孕期两种疾病对先心病具有协同作用。     

膳食钙、磷以及奶制品对绝经后妇女骨密度的影响

目的探讨膳食中钙、磷以及奶制品的摄入量对骨密度及骨盐含量的影响,为研究骨质疏松的预防提供相关线索和依据。方法在广州市越秀区农林街社区发放传单招募调查对象,并采用自编的结构化标准问卷,对320名广州绝经后妇女的膳食习惯进行调查,并测量其全身、股骨全身、股骨颈、股骨干、大粗隆、Ward’s三角以及腰锥1～4的骨密度和骨量,采用多因素逐步回归分析探讨膳食钙、磷及奶制品对骨盐含量及骨密度的影响。结果 320名调查对象平均57.1岁,平均绝经年限7.3年,平均每天摄入钙、磷及奶制品分别为822 mg、949 mg和126 g,平均全身骨密度为1.054 g/cm2,磷与7个部位的骨密度及骨盐含量呈正相关关系（P〈0.05）。随着磷摄入量增加,全身及腰锥1～4骨密度增加,偏回归系数值分别为0.121和0.184 g.（cm2）-1.g-1.d-1。随着奶制品摄入量增加,股骨全身、股骨干骨密度也相应增加,骨密度偏回归系数值分别为0.686、0.841mg.（cm2）-1.g-1.d-1。钙与全身、股骨全身、股骨颈、大粗隆、股骨干和Ward’s三角的BMC具有正相关性,而在钙与BMD关系中,钙只与股骨全身、大粗隆和股骨干呈正相关性,且每日膳食中每增加100 g钙的摄入量,则股骨全身、大粗隆、股骨干的骨密度相应增加5.3、4.8和7.6 g/cm2。结论增加膳食中钙、磷以及奶制品的摄入量有利于绝经后妇女的骨盐含量及骨密度的提高。     

Contribution of thermolabile methylenetetrahydrofolate reductase variant to total plasma homocysteine levels in healthy men and women. Inter99 (2)

Elevation in plasma total homocysteine (tHcy) is believed to be causally related to cardiovascular disease. Like age and sex, the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR(C677T)) is an important nonmodifiable determinant of tHcy, which may be considered when describing normal ranges of tHcy in the general population. We investigated the simultaneous effect of sex, age, and MTHFR(C677T) genotype on the distribution of tHcy in a cross-sectional study design. THcy concentrations and MTHFR(C677T) genotype were determined in a population-based sample of 2,788 Danish men and women aged 30-60 years participating in the Inter99 Study. The prevalences of MTHFR(C677T) genotypes were 48.8% (CC), 42.4% (CT), and 8.8% (TT). The overall median tHcy was 8.1 micromol/l, and the 2.5-97.5 percentiles were 4.8-17.8 micro mol/l. The estimated proportionally higher level of tHcy in men compared to women was 14.3% (P<0.001). A significant interaction term was found between age and MTHFR(C677T) genotype (P<0.001). The estimated changes in tHcy per 5 years of age were 1.5% in CC individuals (P<0.01), 2.1% in CT individuals (P<0.001), and -4.1% in TT individuals (P<0.01). The T allele was associated with elevated tHcy. However, the proportionally higher level of tHcy in TT individuals compared to CT and CC individuals decreased with increasing age. The MTHFR(C677T) polymorphism explained 6% of the phenotypic variation in tHcy. In conclusion, we found that tHcy is associated with sex, age, and MTHFR genotype. Our results indicate that the effect of age is modified by MTHFR genotype.     

Folate status response to controlled folate intake is affected by the methylenetetrahydrofolate reductase 677C-->T polymorphism in young women

This study was designed to evaluate the effect of the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism on folate and homocysteine response in non-Hispanic women consuming a low folate diet followed by a diet providing the Recommended Dietary Allowance (RDA) for folate. Women (aged 20-30 y old) with either the TT (n = 19) or CC (n = 22) MTHFR 677C-->T genotype participated in a folate depletion-repletion study (7 wk, 115 microg dietary folate equivalents (DFE)/d; 7 wk, 400 microg DFE/d). Overall serum folate decreased (P < 0.0001) during depletion and increased (P < 0.0001) during repletion with lower (P = 0.03) postdepletion serum folate in women with the TT versus CC genotype. Folate status was low (serum folate < 13.6 nmol/L) in more women with the TT (59%) compared with the CC genotype (15%) postdepletion. Red blood cell folate for all subjects decreased during depletion (P < 0.0001) and repletion (P = 0.02) with lower (P = 0.04) red blood cell folate in women with the TT compared with the CC genotype postrepletion. Homocysteine increased (P < 0.0001) for both genotype groups postdepletion and decreased (P = 0.02) postrepletion for the CC genotype group only. Homocysteine concentrations tended to be higher (P = 0.09) in the TT versus CC genotype group postdepletion and postrepletion. These data suggest that the MTHFR 677C-->T polymorphism negatively affects the folate and homocysteine response in women consuming low folate diets followed by repletion with the RDA. These results may be important when evaluating the impact of the MTHFR 677C-->T polymorphism in countries in which low folate diets are chronically consumed.     

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.     

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.     

胃癌亚甲基四氢叶酸还原酶基因多态性及其与微卫星不稳的关系

目的探讨胃癌亚甲基四氢叶酸还原酶（MTHFR）基因多态性与微卫星不稳的关系。方法采用聚合酶链反应一限制性片段长度多态性技术检测122例胃癌和101名正常对照的MTHFR基因C677T和A1298C多态性；采用PCR为基础的方法检测微卫星不稳定性（MSI）。结果MTHFR C677T多态性可分为677CC、677CT和677TT三种类型。胃癌组3种基因型频率分别为47．5％、39．3％和13．1％；对照组分别为48．5％、42．6％和8．9％，两组相比差异无统计学意义（P〉0．05）。以677CC基因型做为参考，胃贲门癌677CT基因型OR值为0．38，95％CI：0．15～0．98；TT基因型OR值为0．26，95％CI：0．03～2．18；677CT＋TT基因型OR值为0．36，95％CI：0．07～0．98。胃体癌677TT基因型OR值为3．03，95％CI：1．07～8．65。MTHFR A1298C多态性可分为1298AA、1298AC和1298CC3种类型。胃癌组3种基因型频率分别为59．8％、36．1％和4．1％；对照组分别为57．4％，37．6％和5．0％，两组相比差异无统计学意义（P〉0．05）。以1298AA基因型的OR值为1．00，胃窦癌AC基因型的OR值为0．87，95％CI：0．42～1．82，CC基因型的OR值为0．41，95％CI：0．05～3．72。MTHFR 677TT基因型胃癌与微卫星不稳显著相关（P〈0．05），而MTHFR A1298C多态性与微卫星不稳无关（P〉0．05）。结论重庆地区人群中MTHFR C677T多态性是胃贲门癌的保护因素，是胃体癌的危险因素；MTHFR A1298C多态性可能是胃窦癌的保护因素；677TT基因型胃癌的发生可能涉及到MSI途径。