亚甲基四氢叶酸还原酶基因C677T、G1793A单核苷酸多态性与散发性乳腺癌易感性的关系

目的：研究亚甲基四氢叶酸还原酶（MTHFR）基因C677T、G1793A位点单核苷酸多态性与散发性乳腺癌易感性关系。方法：采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法,对200例乳腺癌患者及200例正常对照者MTHFR基因C677T、G1793A位点单核苷酸多态性进行分析,logistic回归分析不同基因型与乳腺癌风险的关系。结果：乳腺癌组MTHFR 677TT基因型频率为25.00%显著高于正常对照组的10.50%（X2=14.401,P=0.001）,CT基因型频率为44.50%低于正常对照组的54.50%,CC基因型频率在乳腺癌组和正常对照组中无差别;MTHFR 1793GA基因型频率为18.50%显著高于正常对照者的8.50%（X2=8.563,P=0.003）。乳腺癌患者MTHFR 677T和1793A等位基因频率分别为47.25%、9.25%,显著高于对照组中的37.75%、4.25%。MTHFR 677TT基因型携带者罹患乳腺癌的风险是677CC基因型携带者的2.732倍（95%CI=1.418～5.051,P=0.001）,MTHFR1793GA基因型携带者罹患乳腺癌的风险是1793GG基因型携带者的2.444倍（95%CI=1.325～4.505,P=0.003）。另外,乳腺癌组中MTHFR C677T基因多态性与肿瘤大小相关（x2=7.431,P=0.024,MTHFR G1793A基因多态性与淋巴结转移情况（x2=8.939,P=0.011）、癌组织学分级（x2=9.983,P=0.007）相关。结论：MTHFR C677T、G1793A基因多态性与散发性乳腺癌的易感性相关。     

亚甲基四氢叶酸还原酶(C677/T)基因的单核苷酸多态性

亚甲基四氢叶酸还原酶(methylene tetrahydrofolatucte redase,MTHFR)是叶酸代谢过程中的关键酶,对叶酸和同型半胱氨酸的代谢以及DNA的合成、修复与甲基化均有重要作用。MTHFR基因变异导致酶热稳定性及活性降低,引起相关代谢及DNA甲基化异常,进而发生相关疾病。MTHFR具有多种变异型,本文对其中常见的一种C677T的多态性及其与疾病的相关性的研究进展做一综述。     

新疆维吾尔族和汉族亚甲基四氢叶酸还原酶基因多态性研究

目的:研究新疆维吾尔族、汉族两民族亚甲基四氢叶酸还原酶(Methyleneterahyofolate reductase MTHFR)基因多态性的分布情况,获取新疆维吾尔族与汉族MTHFR 1298位群体遗传学数据。方法:应用PCR-RFLP技术检测新疆维吾尔族及汉族MTHFR1298位多态性位点基因频率及基因型频率。结果:新疆维吾尔族、汉族MTHFR 1298位C等位基因分布频率分别为12%、23%,P<0.05有统计学差异性,且新疆维吾尔族MTHFR 1298位C等位基因分布频率与现有报道的少数民族贵州苗族、布依族具有统计学差异。结论:MTHFR 1298位多态性在不同民族具有差异性:MTHFR 1298位多态性在新疆维吾尔族和汉族有民族差异;新疆新疆维吾尔族MTHFR 1298位C等位基因频率与贵州苗族、布依族少数民族之间具有民族差异性。     

亚甲基四氢叶酸还原酶基因（C667T）多态性与糖尿病血管病变

由基因突变引起的MTHFR活性下降会导致血中Hcy水平升高。机体内Hcy水平取决于遗传和环境两方面因素,基因型分析也证明,MTHFR基因纯合突变者和杂合突变者,其血浆Hcy水平高于非突变的正常人。其中,MTHFRC667T突变及其引起的血Hcy升高被认为是引发动脉硬化性血管疾病的一个独立的危险因素。研究显示MTHFR基因多态性与糖尿病微血管病变之间存在着独立相关性。本文就MTHFR基因多态性与糖尿病血管病变的关系及其研究进展做出了简要综述。     

利用LightCycler研究食管鳞状细胞癌与MTHFR C677T多态性的关系

亚甲基四氢叶酸还原酶(MTHFR)在叶酸代谢中起重要作用.MTHFR基因第677位核苷酸的多态性(C→T)能影响其酶活性并与肿瘤易感性有关.为比较中国北方人群MTHFR C677T多态性与食管鳞状细胞癌(ESCC)易感性之间的关系, 通过高速实时聚合酶链反应(real-time PCR)和解链曲线(melting curve)方法分析了189名ESCC患者和141名健康对照的MTHFR C677T多态性位点的基因型.结果显示,健康对照组的MTHFR C/C(纯合野生)、C/T和T/T(纯合突变)基因型的频率分别为17.7%、38.3%和44.0%.ESCC患者的T/T基因型频率(42.3%)与健康对照组无显著差异(χ2=0.089, P＞0.05),其C/T基因型频率(49.2%)仅略高于对照组(χ2＝3.890, P＜0.05),而患者组的C/C基因型频率(8.5%)显著低于健康对照组(17.7%) (χ2=6.37, P=0.012).与C/T和T/T基因型相比,C/C基因型可显著降低ESCC的发病风险(相对风险度的比值比(OR)=0.43, 95%可信区间(CI)=0.22～0.84),在吸烟者和有上消化道肿瘤家族史的患者中这一倾向更加明显.研究提示,在中国北方人群中, MTHFR C677T纯合野生基因型对ESCC的发病起保护作用.     

不明原因复发性自然流产夫妇MTHFR C677T位点多态性分析

目的：分析不明原因复发性自然流产（URSA）夫妇与亚甲基四氢叶酸还原酶基因C677T（MTHFR C677T）位点多态性的关 联性研究。方法：采用聚合酶链式反应- 限制性片段长度多态性( PCR-RFLP)对URSA 组和对照组各50 对夫妇的外周血进行 MTHFR C677T 的位点多态性进行检测分析。结果：URSA 组MTHFR 基因677 位点的T/T、C/T+T/T 基因型的发生频率显著高于 对照组,差异具有统计学意义(P<0.05),而对照组MTHFR 基因677 位点的C/C 基因型发生频率显著高于URSA 组（P<0.05）,两 组MTHFR 基因677 位点的C/T 基因型比较无明显差异（P>0.05)。另外URSA 组等位基因T 明显高于C 的频率,且URSA 组等 位基因T 发生频率显著高于对照组,对照组等位基因C 发生频率显著高于USRA 组,差异均具有统计学意义（P<0.05）。结论： MTHFR C677T 位点的多态性与URSA 的发生密切相关,是该病的重要遗传风险因素。     

MTHFR C677T、A1298C基因多态性与老年单纯收缩期高血压患者Hcy、血脂水平的关系研究

摘要 目的：研究5,10-亚甲基四氢叶酸还原酶（MTHFR）C677T、A1298C基因多态性与老年单纯收缩期高血压（ISH）患者同型半胱氨酸（Hcy）、血脂水平的关系。方法：选取2019年3月至2021年3月期间中南大学湘雅医学院附属海口医院全科医学科收治的212例老年ISH患者作为ISH组,以同期体检无高血压老年人120例为对照组。检测两组MTHFR C677T、A1298C基因多态性。收集两组一般资料及血浆Hcy及血脂检查结果。观察MTHFR C677T、A1298C不同基因型的血浆Hcy、血脂水平差异。采用多因素Logistic回归分析老年ISH发生的影响因素。结果：相比于对照组,ISH组MTHFR C677T位点T等位基因频率较高,C等位基因频率较低;ISH组CC基因型频率较低,CT、TT基因型频率较高（P<0.05）。相比于对照组,ISH组A1298C位点C等位基因频率较高,A等位基因频率较低;ISH组A1298C位点AA基因型频率较低,CC、AC基因型频率较高（P<0.05）。MTHFR基因C677T位点不同基因型血浆Hcy、总胆固醇（TC）水平差异具有显著性（P<0.05）。MTHFR基因A1298C位点不同基因型血浆Hcy、TC水平明显差异具有显著性（P<0.05）。血浆Hcy、MTHFR C677T及A1298C基因多态性是老年ISH发生的影响因素（均P<0.05）。结论：MTHFR C677T、A1298C基因多态性与老年ISH患者血浆TC、Hcy水平有关,血浆Hcy、MTHFR C677T及A1298C基因多态性是老年ISH发生的影响因素。     

利用LightCycler研究食管鳞状细胞癌与MTHFR C677T多态性的关系

亚甲基四氢叶酸还原酶(MTHFR)在叶酸代谢中起重要作用.MTHFR基因第677位核苷酸的多态性（C→T）能影响其酶活性并与肿瘤易感性有关.为比较中国北方人群MTHFR C677T多态性与食管鳞状细胞癌（ESCC）易感性之间的关系, 通过高速实时聚合酶链反应（real-time PCR）和解链曲线（melting curve）方法分析了189名ESCC患者和141名健康对照的MTHFR C677T多态性位点的基因型.结果显示,健康对照组的MTHFR C/C（纯合野生）、C/T和T/T（纯合突变）基因型的频率分别为17.7%、38.3%和44.0%.ESCC患者的T/T基因型频率（42.3%）与健康对照组无显著差异（χ²=0.089, P＞0.05）,其C/T基因型频率（49.2%）仅略高于对照组（χ²＝3.890, P＜0.05）,而患者组的C/C基因型频率(8.5%)显著低于健康对照组(17.7%) (χ²=6.37, P=0.012).与C/T和T/T基因型相比,C/C基因型可显著降低ESCC的发病风险(相对风险度的比值比（OR）=0.43, 95%可信区间（CI）=0.22～0.84),在吸烟者和有上消化道肿瘤家族史的患者中这一倾向更加明显.研究提示,在中国北方人群中, MTHFR C677T纯合野生基因型对ESCC的发病起保护作用.     

MTHFR基因多态性与动脉粥样硬化性脑梗塞的关系

采用ＰＣＲ－ ＲＦＬＰ技术,检测了６２ 例动脉粥样硬化性脑梗塞患者和７９ 名对照者的Ｃ６７７Ｔ 突变的基因型。结果发现, ＭＴＨＦＲ基因Ｃ６７７Ｔ 突变型等位基因（Ｖ）频率在实验组和对照组中,有显著性差异（χ２＝ ４．４１,Ｐ＜ ０．０５）;三种基因型频率在两组人群中均无显著性差异。基因型频率的相对风险分析,ＡＶ基因型比ＡＡ 基因型患脑梗塞风险高１．７６ 倍;ＶＶ 基因型比ＡＡ 基因型患脑梗塞风险高３．２５ 倍。结果表明, ＭＴＨＦＲ 基因Ｃ６７７Ｔ 突变型等位基因与动脉粥样硬化性脑梗塞有一定的关联,突变基因型增加了动脉粥样硬化脑梗塞的发病风险。     

出血性卒中与MTHFR C677T基因多态性的相关性研究

摘要 目的：探讨与分析出血性卒中与亚甲基四氢叶酸还原酶（MTHFR）C677T基因多态性的相关性。方法：2020年2月到2021年4月选择在本地区诊治的H型高血压患者220例作为研究对象,检测所有患者的MTHFR C677T基因多态性状况,检测血清同型半胱氨酸、叶酸、维生素B12含量。随访判定患者的出血性卒中状况并进行相关性分析。结果：随访调查1年,220例患者中出现出血性卒中20例（出血性卒中组）,占比9.1 %。出血性卒中组的血清同型半胱氨酸含量明显高于非出血性卒中组,血清维生素B12、叶酸明显低于非出血性卒中组（P<0.05）。两组的MTHFR C677T基因型分布均符合Hardy-Weinberg遗传平衡,出血性卒中组的TT基因型、等位基因T占比分别为70.0 %、80.0 %,都显著高于非出血性卒中组的24.0 %、35.0 %（P<0.05）。Spearman相关系数分析显示H型高血压患者的血清同型半胱氨酸、叶酸、维生素B12含量、TT基因型、等位基因T都与出血性卒中存在相关性（P<0.05）。多元回归分析显示血清同型半胱氨酸、叶酸、维生素B12含量、TT基因型、等位基因T都为导致H型高血压患者出血性卒中发生的重要因素（P<0.05）。结论：H型高血压在随访过程中容易发生出血性卒中,也伴随有血清同型半胱氨酸、维生素B12、叶酸含量异常,MTHFR C677T的T基因型、等位基因T与出血性卒中存在相关性,也是导致出血性卒中发生的重要危险因素。     

BRCA1 基因启动子区SNPs 与散发性乳腺癌易感性的相关研究

目的:探讨BRCA1基因启动子区rs11655505、rs73625095位点单核苷酸多态性与散发性乳腺癌易感性的关系。方法:采用ASA-PCR方法对200例乳腺癌患者(均经病理确诊)及200例正常女性BRCA1基因启动子区rs11655505(A/G)、rs73625095(A/G)位点单核苷酸多态性(SNP)进行分析,并将其PCR产物进行测序。结果:乳腺癌患者BRCA1基因启动子区rs11655505位点的A/G基因型频率为75%,显著高于正常人的40%;A/A基因型频率为7%,G/G基因型频率为18%,分别低于正常人的30%、30%。此位点的A或G等位基因在乳腺癌病例组及对照组中均无差别(x2=2.427,P=0.119);rs73625095位点的A/G基因型频率为68%,显著高于正常人的15%;G/G基因型频率为32%,低于正常人的84%;乳腺癌病例组中BRCA1基因启动子区rs11655505、rs73625095位点的A/G基因型与淋巴结转移与否相比,差别均有统计学意义(x2=7.321,P=0.026、x2=4.782,P=0.029)。结论:BRCA1基因rs11655505位点、rs736...     

BRCA1基因启动子区SNPs与散发性乳腺癌易感性的相关研究（英文）

目的：探讨BRCA1基因启动子区rs11655505、rs73625095位点单核苷酸多态性与散发性乳腺癌易感性的关系。方法：采用ASA-PCR方法对200例乳腺癌患者（均经病理确诊）及200例正常女性BRCA1基因启动子区rs11655505（A/G）、rs73625095（A/G）位点单核苷酸多态性（SNP）进行分析,并将其PCR产物进行测序。结果：乳腺癌患者BRCA1基因启动子区rs11655505位点的A/G基因型频率为75%,显著高于正常人的40%;A/A基因型频率为7%,G/G基因型频率为18%,分别低于正常人的30%、30%。此位点的A或G等位基因在乳腺癌病例组及对照组中均无差别（x2=2.427,P=0.119）;rs73625095位点的A/G基因型频率为68%,显著高于正常人的15%;G/G基因型频率为32%,低于正常人的84%;乳腺癌病例组中BRCA1基因启动子区rs11655505、rs73625095位点的A/G基因型与淋巴结转移与否相比,差别均有统计学意义（x2=7.321,P=0.026、x2=4.782,P=0.029）。结论：BRCA1基因rs11655505位点、rs73625095位点的A/G基因型可能与散发性乳腺癌的发生相关,而且与有无发生淋巴结转移密切相关。rs73625095位点A和G等位基因可能为散发性乳腺癌发生的遗传危险因素。     

Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer

This study was designed to investigate, in the Turkish population, an association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer. Our study was carried out in 35 patients with gastric cancer (20 men, 15 women) and 144 controls (75 men, 69 women) and 52 colorectal cancer (31 men, 21 women). MTHFR C677T genotypes were determined by polymerase chain reaction, restriction fragment length polymorphism techniques. No differences were observed in the distribution of MTHFR genotypes or allele frequencies in cases versus controls. The homozygous mutation (T/T) in the MTHFR gene was identified in 14.3% of gastric cancer versus 10.4% of controls. MTHFR C677T frequencies of the CC, CT and TT genotypes among colorectal cancer patients were 34.6%, 51.9% and 13.5%, respectively. MTHFR C677T polymorphism may not be important in an individual's susceptibility to gastric and colorectal cancer in Turkey and may not be a useful marker for identifying patients at high risk of developing gastric and colorectal cancer.     

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and susceptibility to gastric adenocarcinoma in an Italian population

Methylenetetrahydrofolate reductase (MTHFR) plays a central role in the metabolism of folate, which provides a methyl donor for DNA methylation and deoxynucleoside synthesis. We performed a case–control study to explore the relationship between two common MTHFR polymorphisms (C677T and A1298C), their combination and interaction with environmental exposures, on gastric adenocarcinoma susceptibility and progression in an Italian population. One hundred and two cases and 254 hospital controls, matched by age and gender, were enrolled. Individuals carrying the MTHFR 677T allele showed an increased risk of gastric cancer (odds ratio (OR) 1.62, 95% confidence interval (CI) 0.98–2.67), particularly among ever smokers (OR 2.10, 95% CI 1.07–5.33) and, among 677 TT individuals, those with a low intake of fruit and vegetables (OR 2.18, 95% CI 1.05–4.54). The strongest effect, however, was noted for the MTHFR 677 TT genotype among the diffuse gastric cancer histotype (OR 2.92, 95% CI 1.12–7.60). No association was detected for the effect of MTHFR A1298C polymorphism. Survival analysis did not show any association between each polymorphism on the overall survival, although when the analysis was restricted to the first year of follow-up after the surgical intervention an improved survival was noted among MTHFR 677 CC subjects compared with the T allele carriers (p value for log-rank test 0.02). In conclusion, MTHFR 677 (any T genotype) appears to modulate an individual's susceptibility to gastric cancer, particularly when combined with cigarette smoking and among those with a low intake of fruit and vegetables. Our results also suggest that an aberrant DNA methylation pattern, through impaired folate metabolism, might play a key role in gastric carcinogenesis. A possible survival effect of the MTHFR C677T genotype in gastric cancer patients deserves further investigations with larger sample sizes.     

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and susceptibility to gastric adenocarcinoma in an Italian population

Methylenetetrahydrofolate reductase (MTHFR) plays a central role in the metabolism of folate, which provides a methyl donor for DNA methylation and deoxynucleoside synthesis. We performed a case-control study to explore the relationship between two common MTHFR polymorphisms (C677T and A1298C), their combination and interaction with environmental exposures, on gastric adenocarcinoma susceptibility and progression in an Italian population. One hundred and two cases and 254 hospital controls, matched by age and gender, were enrolled. Individuals carrying the MTHFR 677T allele showed an increased risk of gastric cancer (odds ratio (OR) 1.62, 95% confidence interval (CI) 0.98-2.67), particularly among ever smokers (OR 2.10, 95% CI 1.07-5.33) and, among 677 TT individuals, those with a low intake of fruit and vegetables (OR 2.18, 95% CI 1.05-4.54). The strongest effect, however, was noted for the MTHFR 677 TT genotype among the diffuse gastric cancer histotype (OR 2.92, 95% CI 1.12-7.60). No association was detected for the effect of MTHFR A1298C polymorphism. Survival analysis did not show any association between each polymorphism on the overall survival, although when the analysis was restricted to the first year of follow-up after the surgical intervention an improved survival was noted among MTHFR 677 CC subjects compared with the T allele carriers (p value for log-rank test 0.02). In conclusion, MTHFR 677 (any T genotype) appears to modulate an individual's susceptibility to gastric cancer, particularly when combined with cigarette smoking and among those with a low intake of fruit and vegetables. Our results also suggest that an aberrant DNA methylation pattern, through impaired folate metabolism, might play a key role in gastric carcinogenesis. A possible survival effect of the MTHFR C677T genotype in gastric cancer patients deserves further investigations with larger sample sizes.     

Methylenetetrahydrofolate reductase C677T mutation in patients with alopecia areata in Turkish population

Objective

Methylene-tetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism and it is thought to influence DNA methylation and nucleic acid synthesis. Mutations in the MTHFR gene have been associated with several autoimmune disorders in previous studies. Alopecia areata (AA) is considered to be a tissue-specific autoimmune disease as the hair follicle has been targeted and antibodies to their own hair follicle structures have been developed. Since there is a common shared pathway between AA and other autoimmune disorders, we aimed to investigate a possible association between the MTHFR gene C677T mutation and AA susceptibility in the Turkish population.

Methods

The study included 136 patients affected by AA and 130 healthy controls. Genomic DNA was isolated and genotyped using a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay for the MTHFR gene C677T mutation.

Results

The distributions of genotype and allele frequencies of MTHFR gene C677T mutation were statistically different between AA patients and the control group (p = 0.036 and p = 0.011, respectively). High differences were also observed when the patients and controls were compared according to CC versus CT + TT (p = 0.012). CT + TT genotypes and T allele of MTHFR gene C677T mutation were found to be a susceptibility factor for AA in the Turkish population.

Conclusion

The results suggest that MTHFR gene C677T mutation may have an effect on the risk of alopecia areata in the Turkish population. This is the first study reporting the association between the MTHFR (C677T) genotype and AA.     

MICB基因多态性与乳腺癌的易感关联性研究

目的:研究海南汉族人群MICB等位基因的多态性与乳腺癌易感性之间的关联性。方法:采用PCRSSP(PCR sequence-specific primers)和PCR-SBT(PCR sequence-based typing)方法对样本MICB等位基因的多态性进行检测。结果:乳腺癌患者中检出14种MICB等位基因;和对照组相比较,MICB*002和MICB*014等位基因在乳腺癌患者组分布频率较少,MICB*002和MICB*014等位基因可能对乳腺癌不易感(MICB*002:OR=0.31,95%CI:0.19-0.51,Pc0.05;MICB*014:OR=0.32,95%CI:0.17-0.60,Pc0.05)。MICB*016和MICB*003等位基因在乳腺癌患者组分布较多;MICB*016和MICB*003等位基因可能对乳腺癌易感(MICB*016:OR=10.68,95%CI:2.52-45.28,Pc0.05;MICB*003:OR=3.57,95%CI:1.34-9.49,Pc0.05);MICB*002/002和MICB*014/014基因型可能对乳腺癌不易感(MICB*002/002:OR=0.12,95%CI:0.04-0.36,Pc0.05;MICB*014/014:OR=0.30,95%CI:0.10-0.89,Pc0.05)。结论:MICB等位基因的多态性与乳腺癌的易感性之间存在关联性。     

The common MTHFR C677T and A1298C variants are not associated with the risk of non-syndromic cleft lip/palate in northern Venezuela

Non-syndromic cleft lip with or without cleft palate （nsCL/P） is among the most common major birth defects, with complex inheritance involving multiple genes and environmental factors. Numerous studies of MTHFR, encoding methylenetetrahydrofolate reductase, which catalyzes the rate-limiting step of folic acid biosynthesis, have shown inconsistent association of two common hypomorphic allelic variants, C677T and A1298C, in nsCL/P patients and, in some cases, their mothers. We have studied the MTHFR C677T and A1298C polymorphisms in nsCL/P patients, their mothers, and population-matched controls from northern Venezuela. We found no evidence for contribution of the MTHFR C677T and A1298C variants to the risk of nsCL/P in northern Venezuela. Overall, our findings fail to support a causal role of either the MTHFR C677T or A 1298C variants in the pathogenesis of nsCL/P in northern Venezuela.     

MTHFR C677T and A1298C gene polymorphisms and their relation to homocysteine level in Egyptian children with congenital heart diseases

Objective

To investigate the association of combined MTHFR C677T and A1298C gene polymorphisms with congenital heart diseases (CHD) in Egyptian children and their mothers and to determine their effect on homocysteine level in these children.

Material and methods

MTHFR C677T and A1298C polymorphisms were genotyped in 160 Egyptian children (80 patients with CHD and 80 healthy controls) and their mothers using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP), while, homocysteine (Hcy) level was measured optically by enzymatic method.

Results

We found that MTHFR 677TT genotype, T allele, 1298CC genotype, and C allele were associated with 2.61, 2.0, 2.91 and 1.99 fold increased risk of CHD in Egyptian children respectively. Furthermore, the frequencies of MTHFR 1298AC and CC genotypes and C allele significantly increased in mothers with CHD affected children. The homocysteine levels were significantly increased in MTHFR 677TT and 1298CC genotypes in children with CHD.

Conclusions

Our study demonstrated an association of MTHFR A1298C polymorphisms with CHD in Egyptian children and their mothers, while, MTHFR C677T polymorphisms were significantly associated with the risk of CHD in the children only. An association between combined MTHFR A1298C and C677T polymorphisms and CHD was recorded in the children and their mothers. Also, homocysteine levels were significantly increased with both MTHFR 677TT and 1298CC genotypes in Egyptian children with CHD.