5,10-亚甲基四氢叶酸还原酶基因多态性与先天性心脏病的关联研究

Correlationship between congenital heart disease and polymorphism of MTHFR gene

目的研究亚甲基四氢叶酸还原酶基因（MTHFR）多位点多态性与先天性心脏病的关联。方法采用病例对照研究,根据样本量计算公式估计样本量,选择2012年12月至2013年11月在山东大学齐鲁儿童医院就诊的150例患有单纯性先心病的患儿为病例组,同期在该院儿保科进行查体的150例正常儿童为对照组,两组儿童性别年龄总体差异无统计学意义。利用聚合酶链反应-限制性片段长度多态性的方法检测两组儿童的MTHFR基因C677T、A1298C、G1793A的基因型及其分布。结果 677位点,与野生型纯合子CC比较,杂合子CT个体患先心病的风险较高（OR=2.249,95%CI 1.305~3.877,Ρ=0.003）,突变纯合子TT个体患先心病的风险是野生型的3.121倍（95%CI 1.612~6.043,P=0.001）。携带突变等位基因T个体的患病风险是野生型C的1.813倍（95%CI 1.310~2.508,P=0.000）。1298位点突变杂合子AC患病风险是野生纯合子AA的2.177倍（95%CI 1.183~4.077,P=0.011）。携带突变等位基因C个体的患病风险是野生型A的2.017倍（95%CI1.128~3.604,P=0.016）。1793位点突变杂合子GA与野生纯合子GG频率在两组分布差异无统计学意义（P=0.145）,等位基因G、A分布差异无统计学意义（Ρ=0.158）。组合基因型分析显示677与1298位点,1298与1793位点对先心病存在联合作用。结论 MTHFR C677T、A1298C突变是先心病的危险因素;MTHFR C677T与A1298C,MTHFR A1298C与G1793A对先心病存在联合作用。

Objective To investigate the association between genetic variations in methylenetetrahydrofolate reductase MTHFR and the risk of congenital heart disease.Methods conducted a case-control study,calculated the sample size by formulas. The sample including 150 isolated CHD cases and 150 controls comparable with the patients in age and sex. They were genotyped for detecting MTHFR C677 T,A1298C,G1793 A polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis（ PCR-RFLP） methods. Results For the 677,compared with wild CC genotype,heterozygosity CT increased the risk of CHD（ OR = 2. 249,95% CI 1. 305- 3. 877,P =0. 003）, the homozygous mutant genotype TT was associated with the risk of CHD significantly（ OR = 3. 121,95% CI 1. 612- 6. 043,P = 0. 001）. Compared with the wild allete,mutant allete increased the risk of CHD by 1. 813（ 95% CI 1. 310- 2. 508,P =0. 000）. For the 1298,Compared with wild AA genotype,heterozygosity AC increased the risk of CHD（ OR = 2. 177,95% CI 1. 183- 4. 077,P = 0. 011）. The mutant allete C increased the risk of CHD by 2. 017（ 95% CI 1. 128- 3. 604,P = 0. 016）. For the 1793,The proportion of the heterozygote GA and homozygote AA had no statistical differences in the two groups（ P = 0. 145）,also the mutant allete and wild allete（ P = 0. 158）. There were joint effects of MTHFR C677 T and MTHFR A1298 C,MTHFR A1298 C and MTHFR G1793 A. Conclusion Genetic polymorphisms in MTHFR C677 T and MTHFR A1298 C might contribute to the risk of developing CHD,joint effects were found of MTHFR C677 T and MTHFR A1298 C,MTHFR A1298 C and MTHFR G1793 A.