Xu Jing, Xu Xiaohan, Xue Lei, Liu Xiang, Gu Haiyong, Cao Hailong, Qiu Wanshan, Hu Zhibin, Shen Hongbing, Chen Yijiang
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Peoples Republic of China.
Cardiol Young. 2010 Jun;20(3):318-26. doi: 10.1017/S1047951110000247. Epub 2010 Apr 7.
To investigate whether genetic variants in methylenetetrahydrofolate reductase (MTHFR) and methylenetetrahydrofolate dehydrogenase (MTHFD) genes are associated with risk of congenital cardiac disease.
Accumulative evidence suggests that hyperhomocysteinaemia is associated with risk of congenital cardiac disease. Inherited polymorphisms in key folate metabolic pathway genes, MTHFR and MTHFD, may influence the efficiency of folate metabolism and plasma level of homocysteine.
A two-stage case-control study of congenital cardiac disease was conducted by genotyping MTHFR c.1793G>A and four other variants - MTHFR c.677C>T, c.1298A>C, and MTHFD c.1958G>A, c.401C>T - in a Chinese population consisting of 1033 congenital cardiac disease patients and 1067 non-congenital cardiac disease patients.
The variant genotypes of MTHFR c.1793GA/AA were associated with a significantly decreased risk of congenital cardiac disease in two stages combined, with an adjusted odds ratio of 0.67 and a 95% confidence interval of 0.54-0.84 (p = 0.0004). In comparison with wild-type homozygote c.1793GG, the effect was significant in isolated perimembranous ventricular septal defect patients with an adjusted odds ratio of 0.60 and a 95% confidence interval of 0.43-0.83 (p = 0.0003).
These findings indicate that MTHFR c.1793G>A may have a role in susceptibility to sporadic congenital cardiac disease.
研究亚甲基四氢叶酸还原酶（MTHFR）和亚甲基四氢叶酸脱氢酶（MTHFD）基因的遗传变异是否与先天性心脏病风险相关。
越来越多的证据表明，高同型半胱氨酸血症与先天性心脏病风险相关。关键叶酸代谢途径基因MTHFR和MTHFD的遗传多态性可能会影响叶酸代谢效率和同型半胱氨酸的血浆水平。
对1033例先天性心脏病患者和1067例非先天性心脏病患者组成的中国人群进行了一项两阶段先天性心脏病病例对照研究，对MTHFR基因c.1793G>A以及其他四个变异体——MTHFR基因c.677C>T、c.1298A>C和MTHFD基因c.1958G>A、c.401C>T进行基因分型。
MTHFR基因c.1793GA/AA变异基因型在两个阶段合并分析时与先天性心脏病风险显著降低相关，校正比值比为0.67，95%置信区间为0.54 - 0.84（p = 0.0004）。与野生型纯合子c.1793GG相比，在孤立性膜周部室间隔缺损患者中该效应显著，校正比值比为0.60，95%置信区间为0.43 - 0.83（p = 0.0003）。
这些发现表明MTHFR基因c.1793G>A可能在散发性先天性心脏病易感性中起作用。
