亚甲基四氢叶酸还原酶基因多态性与乳腺癌化疗敏感性的关系

目的观察叶酸代谢的关键酶亚甲基四氢叶酸还原酶（MTHFR）基因C677T、A1298C多态与乳腺癌患者对化疗敏感性的关系。方法收集经病理学确诊的晚期乳腺癌患者61例，所有病例化疗前抽静脉血，提取白细胞DNA，用PCR—RFLP技术检测MTHFR基因型。接受6种不同的化疗方案化疗。结果61例乳腺癌癌患者中，MTHFRC／C基因型17例（27．9％）、C／T29例（47．5％）、T／T15例（24．6％）。MTHFR A1298C A／A基因型42例（68．9％），17例（27．9％）A／C基因型，2例（3．3％）C／C基因型。化疗总有效率为67．2％（41／61），其中CR3例（4．9％），PR38例（62．3％），SD15例（24．6％），PD5例（8．2％）。6种化疗方案的有效率无统计学差异（P=0．397）。MTHFRC／C基因型、C／I＂基因型、T／]r基因型的有效率分别为58．8％、58．6％、93．3％，T/T基因型患者的有效率显著高于C／C基因型（P=0．041）和C／T基因型患者（P=0．034）。MTHFR A1298C A／A基因型、A／C基因型、C／C基因型的有效率分别为71．4％、64．7％、0．0％，MTHFR A1298C A／A基因型患者的有效率与A／C基因型（P=0．756）、C／C基因型患者之间无统计学差异（P=0．096）。结论本研究初步结果显示MTHFR C677T基因多态性对预测乳腺癌化疗疗效具有较好的临床应用价值。     

亚甲基四氢叶酸还原酶基因多态性与乳腺癌新辅助化疗敏感性关系的研究探讨

目的研究叶酸代谢的关键酶亚甲基四氢叶酸还原酶（MTHFR）基因C677T、A1298C多态与乳腺癌患者对新辅助化疗敏感性的关系。方法收集经病理学或细胞学确诊的乳腺癌患者61例,均给予新辅助化疗。接受环磷酰胺、表阿霉素、5-氟尿嘧啶联合化疗方案（CAF）化疗34例,表阿霉素、紫杉醇联合化疗方案（AT方案）化疗27例。所有病例化疗前抽静脉血,提取白细胞DNA,用聚合酶链反应限制性片段长度多态性（PCR-RFLP）技术检测MTHFR基因型。化疗后均测量肿块大小进行疗效评价,手术均行病理检查,观察化疗反应分级情况。结果 61例乳腺癌患者中,使用CAF方案和AT方案的临床有效率分别为61.5%、75.0%,差异无统计学意义;Ⅰ~Ⅲ级化疗反应率分别为55.9%、74.1%,差异无统计学意义。携带MTHFR C677T T/T基因型、C/T基因型、C/C基因型的乳腺癌患者化疗的临床有效率分别为83.3%、72.4%、42.9%,Ⅰ~Ⅲ级化疗反应率分别为83.3%、65.5%、35.7%。携带T/T基因型乳腺癌患者的临床有效率和Ⅰ~Ⅲ级化疗反应率均显著高于携带C/C基因型的患者,而与携带C/T基因型患者相比差异无统计学意义。携带MTHFR A1298C A/A基因型、A/C基因型、C/C基因型的乳腺癌患者化疗的临床有效率分别为70.5%、64.7%、0.0%,Ⅰ~Ⅲ级化疗反应率分别为70.5%、47.1%、0.0%。携带MTHFR A1298C A/A基因型患者的临床有效率和Ⅰ~Ⅲ级化疗反应率与A/C及C/C基因型患者之间差异均无统计学意义。结论 MTHFR C677T基因多态性的作用与乳腺癌新辅助化疗敏感性之间存在着一定的相关性,对预测乳腺癌新辅助化疗的疗效具有良好的临床应用前景。     

急性淋巴细胞白血病患儿亚甲基四氢叶酸还原酶基因多态性与甲氨蝶呤动态血药浓度相关性的研究

目的本研究旨在探讨亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C基因多态性对急性淋巴细胞白血病(ALL)患儿使用大剂量甲氨蝶呤(HD-MTX)化疗期间的MTX动态血药浓度的相关关系。方法 35例ALL患儿外周血,提取基因DNA,应用PCR-RFLP方法检测MTHFR C677T、A1298C基因型;应用荧光偏振免疫分析法(FPIA)24h、48h、72h监测患儿外周血中甲氨蝶呤动态血药浓度。结果 MTHFR C677T各基因型间24 h MTX浓度有差异(P0.05),携带CT型者明显高于携带CC型和TT型者;MTHFR C677T各基因型48 h、72 h的MTX浓度未见差异。MTHFR A1298C各基因型24 h、48 h7、2 h的MTX浓度未见差异(P0.05)。结论 MTHFR C677T基因多态性影响ALL患儿HD-MTX化疗期间MTX血药浓度,提示在HD-MTX治疗时可根据检测MTHFR C677T基因型进行个体化治疗。     

MTHFR(C677T,A1298C和G1793A)基因多态性对死胎的影响

目的评估亚甲基四氢叶酸还原酶(methylenetetrahydrofolate recuctase,MTHFR)C677T,A1298C和G1793A基因多态性与死胎的关系。方法收集2014年8月~2016年8月延安大学附属医院33例出现不明原因死胎的妇女和582例正常活胎的妇女进行病例对照研究。使用PCR-RFLP法检测MTHFR基因C677T,A1298C和G1793A多态性,通过logistic回归分析MTHFR基因多态性与死胎易感性之间的关系。结果病例组与对照组MTHFR A1298C和G1 793A多态性位点的基因型频率间不存在显著性差异,但是多态性位点C677T的突变基因型频率间存在显著性差异(CT:P=0.02,x~2=3.67;TT:P=0.02,x~2=3.65),杂合子CT和纯合子TT可能是死胎发生的高风险因子。MTHFR C677T突变基因型在早期死胎中出现1例(14.3%,1/7),在晚期死胎中出现3例(11.5%,3/26),两组差异无统计学意义。双胎妊娠使死胎风险增加8倍(P0.001,x~2=13.28),MTHFR C677T的存在使死胎的风险增加了3.4倍(P=0.02,x~2=3.65)。结论 MTHFR C677T基因多态性是死胎发生的危险因素,可以作为妊娠患者出现死胎现象的预后指标。     

探讨MTHFR基因多态性与新疆地区人群唇腭裂发病的关系

目的 探讨亚甲基四氢叶酸还原酶（MTHFR）基因C677T和A1298C多态性与新疆地区部分人群非综合征性唇腭裂（NSCL/P）发病的关系.方法 采用病例对照设计,试验组为新疆地区NSCL/P患儿44例（维吾尔族12例,汉族32例）;对照组为非唇腭裂患儿62例（维吾尔族26例,汉族36例）.应用聚合酶链式反应-限制性片段长度多态性方法（PCR-RFLP）对MTHFR基因C677T和A1298C进行多态性检测.结果 新疆地区汉族NSCL/P的MTHFR C677T和A1298C位点基因型及等位基因频数与对照组差异无统计学意义（x2=0.07,P ＞0.05;X2 =0.30,P＞0.05）;维吾尔族NSCL/P的MTHFR C677T位点基因型及等位基因频数与对照组差异无统计学意义（X2=0.12,P ＞0.05）,而MTHFR A1298C位点基因型及等位基因频数与对照组比较其差异有统计学意义（X2=8.90,P ＜0.01）.结论 新疆地区汉族MTHFR基因C677T和A1298C位点多态性可能与NSCL/P的发生无关;维吾尔族MTHFR基因C677T位点多态性与NSCL/P的发生可能无关,而A1298C位点多态性与NSCL/P的发生相关,可能是NSCL/P发病的易感因素.     

陕西省延安地区育龄女性MTHFR基因多态性和国内多地区相关报道比较分析2)

目的分析陕西省延安地区育龄女性叶酸代谢关键酶亚甲基 四氢叶酸还原酶(MTHFR)的基因多态性及地区遗传分布特征。方法 以延安市第二医疗集团1 508例育龄女性为研究对象,用荧光定量PCR法检测其MTHFR C677T ,A1298C基因位点多态性,并和国内多地区相关报道比较分析。结果”K 该地区三种表现型正常型、较弱型和弱型分别占22.5%,50.7%和26.8%。MTHFR C677T 位点CC,CT和TT基因频率分别为24.7%,48.6%和26.7%;MTHFR A1298C位点AA,AC和CC基 因频率分别为71.0%,26.7%和2.3%,与已报道的南方城市湘潭、武汉、南宁等地区相比 ,差异均有统计学意义( P <0.05)。MTHFR C677T和A1298C等位基因分布情况与其基因型 分布情况类似。结论该地区育龄女性MTHFR基因以基因型(MTHFR C6 77T/A1298C)CT/AA型为主,MTHFR C677T TT纯合突变型呈现北高南低的趋势,其T等位基因 频率也呈现随纬度的递减而降低的走向。     

育龄女性MTHFR、MTRR基因多态性分布以及与血清叶酸和同型半胱氨酸水平的相关性研究

目的探讨叶酸代谢关键酶基因5,10-亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C和甲硫氨酸合成酶还原酶(MTRR)A66G多态性在育龄女性中的分布特征,并分析不同遗传特征对外周血叶酸和同型半胱氨酸(Hcy)水平的影响。方法选取2018年3月至2020年1月在上海计生所医院妇科就诊的汉族育龄女性2 651例,根据知情同意原则,采集口腔黏膜上皮脱落细胞,抽提基因组DNA,使用荧光定量PCR方法检测MTHFR C677T、A1298C和MTRR A66G基因多态性,采用化学发光法检测外周血叶酸水平,循环酶法检测血清Hcy水平。结果 (1)MTHFR C677TCC、CT、TT的基因型频率分别为33.2%、47.9%、18.9%,C、T等位基因频率分别为57.1%、42.9%;MTHFR A1298C AA、AC、CC的基因型频率分别为66.6%、30.5%、2.9%,A、C等位基因频率分别为81.8%、18.2%;MTRR A66G AA、AG、GG的基因型频率分别为56.4%、36.9%、6.8%,A、G等位基因频率分别为74.8%、25.2%。(2)MTHFR C677T和A1298C两位点连锁有7种组合,频率最高的是CT/AA(31.9%),没有CT/CC和TT/CC组合。两位点间存在完全连锁不平衡(D′=0.984,R2=0.161)。(3)MTHFR C677T不同基因型的叶酸和Hcy水平差异有统计学意义(P<0.05)。TT基因型的叶酸水平低于CC基因型,TT基因型的Hcy水平高于CC基因型。经单因素Logistic回归分析发现,MTHFR C677T TT基因型发生高Hcy血症的危险性是CC基因型的9.97倍(95%CI:3.81~26.05)。MTHFR A1298C和MTRR A66G不同基因型与血清叶酸及Hcy水平差异无统计学意义(P>0.05)。(4)经单因素回归分析,Hcy水平与叶酸水平呈负相关(R2=0.061,P<0.05),叶酸水平可解释Hcy水平个体差异的6.1%。结论获取了上海市汉族育龄女性MTHFR和MTRR基因多态性的群体遗传学特征,血清Hcy水平与MTHFR C677T基因多态性以及血清叶酸水平有关。筛查MTHFR和MTRR基因多态性并监测Hcy水平对围生期保健有重要的指导意义。     

陕西省延安地区育龄女性MTHFR基因多态性和国内多地区相关报道比较分析

目的分析陕西省延安地区育龄女性叶酸代谢关键酶亚甲基四氢叶酸还原酶(MTHFR)的基因多态性及地区遗传分布特征。方法以延安市第二医疗集团1 508例育龄女性为研究对象,用荧光定量PCR法检测其MTHFR C677T,A1298C基因位点多态性,并和国内多地区相关报道比较分析。结果该地区三种表现型正常型、较弱型和弱型分别占22.5%,50.7%和26.8%。MTHFR C677T位点CC,CT和TT基因频率分别为24.7%,48.6%和26.7%;MTHFRA1298C位点AA,AC和CC基因频率分别为71.0%,26.7%和2.3%,与已报道的南方城市湘潭、武汉、南宁等地区相比,差异均有统计学意义(P0.05)。MTHFR C677T和A1298C等位基因分布情况与其基因型分布情况类似。结论该地区育龄女性MTHFR基因以基因型(MTHFR C677T/A1298C)CT/AA型为主,MTHFR C677TTT纯合突变型呈现北高南低的趋势,其T等位基因频率也呈现随纬度的递减而降低的走向。     

长寿地区73例结节性甲状腺肿患者MTHFR基因C677T和A1298C多态性研究

目的研究重庆长寿地区人群中结节性甲状腺肿(NG)与亚甲基四氢叶酸还原酶(MTHFR)基因C677T(rs1801133)、A1298C(rs1801131)位点单核苷酸多态性的关系。方法选取重庆市长寿区人民医院73例NG患者(病例组)和76例体检健康者(对照组),采用一代Sanger测序技术对受试者的全血标本进行DNA测序。结果病例组中年龄>30岁的患者占96.05%,>60岁的占23.68%。对照组中年龄>30岁的占97.56%,>60岁的占19.51%。病例组与对照组年龄、性别比较,差异无统计学意义(P>0.05)。病例组、对照组及病例组+对照组基因型C677T、A1298C男女分布比较,差异均无统计学意义(P>0.05)。MTHFR(A1298C)C等位基因(OR=0.397,95%CI:0.161~0.981,P=0.041)和CC基因型(OR=0.116,95%CI:0.014~0.978,P=0.027)降低NG发生的风险,MTHFR C677T多态性与NG的发生没有相关性。结论A1298C基因多态性与NG发生风险有关;MTHFR基因C677T位点的多态性与NG发生风险无关。     

中老年高同型半胱氨酸血症基因多态性与叶酸治疗效果的关联性研究

目的 探讨中老年高同型半胱氨酸血症(HHcy)相关基因多态性与叶酸补充效果的关联性。方法 2020年1~12月于宜宾市第一人民医院确诊的中老年HHcy患者334例,采用问卷收集一般资料,抽取清晨空腹血测定同型半胱氨酸(Hcy)浓度,采用PCR荧光探针法和实时定量荧光PCR(RT-PCR)法检测外周血基因组DNA中MTHFR基因C677T(rs1801133)、A1298C(rs1801131)和MTRR基因A66G (rs1801394)多态性位点,比较不同情况HHcy患者MTHFR基因C677T、A1298C和MTRR基因A66G基因型构成比和等位基因频率。结果 MTHFR基因C677T位点TT型、A1298C位点CC型和MTRR基因A66G位点GG型占比分别为46.7%、16.2和13.5%,rs1801133 T等位基因、rs1801131 C等位基因和rs1801394 G等位基因占比分别为63.3%、29.0%和29.0%。不同居住地、民族和吸烟饮酒史的rs1801131基因型分布比较,差异有统计学意义(P<0.05),不同居住地、BMI及吸烟饮酒史的rs1801394基因型分布比较,差异有统计学意义(P<0.05)。叶酸治疗无效组MTHFR基因T677T和C1298C频率及rs1801133 T等位基因和rs1801131 C等位基因频率高于有效组(P<0.05)。结论 MTHFR的T677T和C1298C患者叶酸治疗效果差。     

河南汉族人群MTHFR基因多态性与肺癌的关系

目的 探讨河南地区汉族人群5,10-亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR）氨基酸突变位点C677T和A1298C基因多态性分布与肺癌发生的关系。方法 202例肺癌患者（肺癌组）和202例体检健康者（对照组）,2组采用限制性片段长度多态性酶切技术检测MTHFR基因型,分析MTHFR基因C677T和A1298C位点基因频率分布特点。结果 肺癌组MTHFR基因C677T位点CC、CT、TT基因亚型分布频率分别为26.7%、50.5%、22.8%,对照组分别为34.2%、55.4%、10.4%,CC、CT亚型与对照组比较差异无统计学意义（P〉0.05）,TT基因亚型与对照组比较差异有统计学意义（P〈0.05）;携带TT基因型患肺癌的风险比值比为2.542,95%CI为1.453~4.444;肺癌组MTHFR基因A1298C位点AA、AC、CC基因亚型分布频率分别为27.2%、52.5%、20.3%,对照组分别为32.2%、50.5%、17.3%,2组比较差异均无统计学意义（P〉0.05）。结论 MTHFR基因C677T基因TT亚型与肺癌的发病明显相关,未发现A1298C基因多态性与肺癌的发生有相关性。     

消化道肿瘤患者MTHFR 基因多态性与5- 氟尿嘧啶化疗不良反应的相关性研究

目的　在消化道肿瘤患者中,探讨MTHFR 1298A>C 和MTHFR 677C>T 基因多态性与5- 氟尿嘧啶（5-FU） 化疗出现不良反应的关系。方法　2016 年2~6 月,入组复旦大学附属中山医院肿瘤内科收治的123 例消化道肿瘤患 者。提取外周血中的基因组DNA,通过Sanger 测序检测MTHFR 1298A>C 和MTHFR 677C>T 的基因型。随访其中 98 例含5-FU 治疗方案的患者,分析了不同基因型的患者发生毒副反应的类型及严重程度的区别。结果　123 例消化道 肿瘤患者中,MTHFR 1298A>C 野生型 76 例（61.79%）,杂合型AC 40 例（32.52%）,纯合型CC 7 例（5.69%）。 MTHFR677C>T 野生型CC 50 例（40.65%）, 杂合型CT 61 例（49.59%）, 纯合型TT 12 例（9.76%）。98 例化疗 方案中含5-FU 的患者中,MTHFR 677C>T 突变型（CT 和TT）显著增加化疗后发生不良反应的风险（χ2=4.188, P<0.05）;MTHFR 1298A>C 突变型（AC 和AA）、性别、年龄、治疗方案与使用5-FU 产生的相关毒副作用无显著关 联性。结论　在接受5-FU 治疗的消化道肿瘤患者中,MTHFR 677C>T 多态性显著增加化疗相关毒副反应的发生风险, 该基因可能成为预测氟尿嘧啶类化疗药物发生临床不良事件的风险因素,能够为临床选择合适的治疗方案提供更多的信 息。     

Easy detection of 5,10-methylenetetrahydrofolate reductase 1298A/C genotype by mutagenically separated PCR assay.

BACKGROUND: 5,10-Methylenetetrahydrofolate reductase (MTHFR) plays a central role in folate metabolism. Previous studies have suggested an association between the MTHFR 1298A/C polymorphism and several diseases, such as cardiovascular and psychiatric diseases, neural tube defects, diabetes, and cancer. Currently, either PCR-restriction fragment length polymorphism (RFLP) technique or real-time PCR using Taqman assay are used to determine the MTHFR 1298 genotype. METHODS: We developed a simple and efficient approach that employs mutagenically separated PCR to genotype MTHFR 1298A/C polymorphism. Two forward mutagenic allele-specific primers of different lengths for MTHFR 1298A/C were paired with the same reverse primer in a one-tube assay to genotype 20 genomic DNA samples. RESULTS: Electrophoresis on 2.5% agarose gel showed two allele-specific fragments, a 113-bp A allele-specific and a 93-bp C allele-specific PCR product. The results were confirmed by the conventional PCR-RFLP method. CONCLUSIONS: We conclude that mutagenically separated PCR could be used as an alternative simple, reliable, and cost-effective method for the genotyping of MTHFR 1298A/C polymorphism.     

Patterns of co-occurrence of three single nucleotide polymorphisms of the 5,10-methylenetetrahydrofolate reductase gene in kidney transplant recipients

BACKGROUND: Recently, a new mutation of the 5,10-methylenetetrahydrofolate reductase (MTHFR) encoding gene was first described (1793G > A). Only few reports have studied the prevalence of this polymorphism, especially in combination with other MTHFR mutations (677C > T, 1298A > C). METHODS: We cross-sectionally identified the novel MTHFR 1793G > A polymorphism in 730 kidney transplant recipients. MTHFR 677C > T and 1298A > C were also assessed and the frequency of each was described individually as well as in cross-tabulation with the other MTHFR genotypes. The expected number of patients for each MTHFR genotype combination was calculated and contrasted with the observed numbers. Fisher's exact test was used for statistical inference. RESULTS: The allelic frequency of MTHFR 1793G > A was 0.052. Seventy-two patients (9.9%) were heterozygous and two patients (0.3%) were homozygous. From the cross-tabulations, we identified 53 patients (expected: 33.6) with the MTHFR 1298AC/1793GA genotype and 17 patients (expected: 6.7) with the MTHFR 1298CC/1793GA genotype. Furthermore, we found two patients with double homozygosity for MTHFR 1793G > A and MTHFR 1298A > C (MTHFR 1793AA/1298CC genotype). The frequencies of these genotype combinations were substantially larger than could be expected (P < 0.001). CONCLUSIONS: These findings suggest a selection or survival advantage for individuals with combined MTHFR 1793G > A and MTHFR 1298A > C genotypes, possibly owing to a mutually stabilizing effect on MTHFR enzyme activity.     

影响亚甲基四氢叶酸还原酶和甲硫氨酸合成酶还原酶基因多态性的因素分析

目的了解影响女性亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C位点和甲硫氨酸合成酶还原酶(MTRR)A66G位点基因多态性的因素。方法采用横断面调查研究方法,以湖北省内1 902例女性为对象,采集口腔黏膜上皮细胞,提取DNA,用实时荧光定量PCR技术检测MTHFR和MTRR基因,统计分析不同民族MTHFR和MTRR基因多态性的差异,与其他地区人群的MTHFR和MTRR基因多态性进行比较,并分析不同位点基因多态性之间的关联关系。结果 (1)湖北省汉族女性和少数民族女性在MTHFR C677T和MTRR基因多态性构成差异无统计学意义(P>0.05),而MTHFR A1298C位点基因多态性构成差异有统计学意义(P<0.05)。(2)MTHFR C677T位点的纯合突变基因型TT的频率从南到北呈上升趋势,MTHFR A1298C位点的纯合突变基因型CC的频率从南到北呈下降趋势,而MTRR A66G位点基因多态性在不同地区差异不大。(3)MTHFR C677T位点的纯合突变基因型TT的频率在A1298C位点的正常型、杂合型、纯合突变型中分别为15.9%、0.1%、0.0%,差异有统计学意义(P<0.01);MTHFR C677T位点的纯合突变基因型TT的频率在MTRR A66G位点的正常型、杂合型、纯合突变型中分别为9.4%、5.9%、0.7%,差异无统计学意义(P>0.05)。结论 MTHFR A1298C位点基因多态分布存在民族差异;而MTRR C677T、A1298C位点基因多态分布存在地区差异;同一基因不同位点的基因多态性有关联。     

C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene: incidence and effect of combined genotypes on plasma fasting and post-methionine load homocysteine in vascular disease

BACKGROUND: Moderately increased plasma concentrations of total homocysteine (tHcy) have been shown to be an important risk factor for vascular diseases. Two common polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, the thermolabile C677T and a more recently reported A1298C polymorphism, may contribute to hyperhomocysteinemia. METHODS: Using PCR and restriction fragment length polymorphism analysis, we studied the prevalence of the C677T and A1298C MTHFR genotypes and the combined effect of these polymorphisms on plasma tHcy concentrations, as measured by HPLC with fluorometric detection, both fasting and post-methionine load (PML), in 1238 individuals. RESULTS: The prevalences of the C677T and A1298C genotypes did not differ significantly in 772 individuals with documented coronary artery disease (CAD), 137 individuals with deep-vein thrombosis (DVT), and 329 individuals without documented vascular disease. Individuals homozygous for the 677T allele had significantly increased fasting tHcy, particularly in the presence of low folate, compared with individuals homozygous for the wild-type allele. Neither the 1298AC nor the 1298CC genotype was associated with significantly increased fasting or PML tHcy concentrations irrespective of serum folate. Of the nine combined MTHFR genotypes, six were present in >10% of the population. Of these, the difference in mean fasting tHcy reached statistical significance (P<0.005) only in individuals with the 677TT/1298AA genotype compared with individuals with the wild-type 677CC/1298AA genotype. Differences in mean fasting tHcy did not reach statistical significance in individuals heterozygous for both MTHFR variants. We detected two 677CT/1298CC and three 677TT/1298AC individuals; only one, an 677TT/1298AC individual, had increased tHcy (both fasting and PML). No individuals had the 677TT/1298CC genotype. CONCLUSIONS: The prevalences of the C677T and A1298C polymorphisms did not differ among individuals with CAD, DVT, or those without documented vascular disease. In contrast to the C677T polymorphism, the A1298C polymorphism is not associated with increased fasting tHcy. Although the two polymorphisms usually exist in trans configuration, crossover may occur rarely to form recombinant chromosomes.     

Metabolic effects of C677T and A1298C mutations at the MTHFR gene in Brazilian children with neural tube defects

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) deficiency leads to impairment in folate metabolism and is implicated as a risk factor for neural tube defects (NTDs). Both C677T and A1298C MTHFR mutations are associated with NTDs, in some populations. METHODS: The frequencies of the C677T and A1298C MTHFR mutations were determined in 25 children with NTDs, case mothers and 75 healthy individuals from Sao Paulo City. Both C677T and A1298C mutations were analyzed by PCR-FLRP. The effects of MTHFR mutations on folate, vitamin B12 and homocysteine concentrations were also evaluated. RESULTS: C677T and A1298C allele frequencies in NTDs children and mothers were similar to that found in controls. Eleven in 23 NTDs patients and 10 in 21 NTDs mothers had folate or vitamin B12 concentrations in the lower end of the normal range. In NTDs children, C677T MTHFR genotypes did not affect vitamins and homocysteine concentrations, but plasma homocysteine was higher (p=0.028) in patients with 1298AA MTHFR genotype. Moreover, 677CT/1298AA haplotype was associated with lower vitamin B12 concentrations (p<0.05) in NTDs children. CONCLUSIONS: MTHFR gene mutations may affect vitamin B12 and homocysteine metabolism in Brazilian children with NTDs.