Association of the C677T methylenetetrahydrofolate reductase mutation with congenital heart diseases
Association of the C677T methylenetetrahydrofolate reductase mutation with congenital heart diseases
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DOI：
10.1111/j.0001-6349.2005.00611.x
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发表时间：
2005-12-01
影响因子：
4.3
通讯作者：
Hsieh, FJ
中科院分区：
文献类型：
--
作者：
Lee, CN;Su, YN;Hsieh, FJ
目的应用变性高效液相色谱技术，通过高通量异源双链分析，探讨亚甲基四氢叶酸还原酶（MTHFR）基因第677位碱基的胞嘧啶-胸腺嘧啶突变是否与先天性心脏病（CHD）相关。我们调查了213例经心导管检查证实的冠心病患者和195例健康对照者的MTHFR基因型。MTHFR C677 T多态性基因型频率在冠心病组和健康对照组间差异无统计学意义（P=0.345）。此外，考虑到CHD患者的不同亚组，我们注意到患有肺动脉瓣狭窄（PS）或肺动脉闭锁伴室间隔完整（PA + IVS）的患者中纯合子TT基因型的比例显著增加（p = 0.0005）。对于表现为异位综合征、圆锥动脉干异常（包括法洛四联症、主动脉弓中断、永存动脉干和肺动脉窗）的患者，差异无统计学意义。MTHFR基因型在CHD各亚型中分布的差异反映了CHD发病机制的异质性。TT纯合子基因型比例的增加可能与瓣膜PS和PA + IVS的发病有关。
Background To investigate whether the cytosine-to-thymine mutation at base 677 of the gene for methylenetetrahydrofolate reductase (MTHFR) is associated with congenital heart diseases (CHD), using high throughput heteroduplex analysis based upon the powerful technique of denaturing high-performance liquid chromatography.Methods. We investigated the MTHFR genotype of a cytosine-to-thymine mutation at base 677 for 213 patients of CHDs as confirmed by cardiac catheterization and also for 195 healthy controls.Results. The overall genotype frequencies of the MTHFR C677T polymorphism were not significantly different between the CHD patients and the healthy control (P=0.345). Furthermore, taking various subgroups of CHD patients into consideration, we noted a significantly increased proportion of homozygous TT genotypes for patients suffering from valvular pulmonary stenosis (PS) or pulmonary atresia with an intact ventricular septum (PA + IVS) (p = 0.0005). For patients revealing heterotaxy syndrome, a conotruncal anomaly including tetralogy of Fallot, an interruption of the aortic arch, persistent truncus arteriosus, and aortopulmonary window, no statistically significant difference existed.Conclusions. The discrepancy in the distribution of MTHFR genotypes amongst various subtypes of CHD reflects some heterogeneity in the developmental mechanism of CHD. The increased percentage of homozygous TT genotypes might contribute to the pathogenesis of valvular PS and PA + IVS.