5,10-亚甲基四氢叶酸还原酶基因多态性与先天性心脏病关系

目的 探讨5，10-亚甲基四氢叶酸还原酶（MTHFR）基因多态性与先天性心脏病（CHD）的关系，为CHD的防治提供参考依据。方法 采用以医院为基础的病例对照研究方法抽取2012年12月-2013年11月山东大学齐鲁儿童医院就诊的150例患有单纯性CHD的患儿及同期在该医院儿童保健科进行查体的150名健康儿童分别作为病例组和对照组，检测2组儿童MTHFR基因C677T、A1298C、G1793A的基因型及其分布。结果 MTHFR C677T位点T等位基因儿童患CHD的风险为C等位基因的1.813倍（χ²=12.990，P=0.000），CT、TT、CT+TT基因儿童患CHD的风险分别为CC基因的2.249、3.121、2.489倍（P<0.01）；MTHFR A1298C位点C等位基因儿童患CHD的风险为A等位基因的2.017倍（χ²=5.785，P=0.016），AC基因儿童患CHD的风险为AA基因的2.177倍（χ²=6.434，P=0.011）；MTHFR G1793A位点G与A等位基因和GG与GA基因儿童患CHD的风险差异均无统计学意义（均P>0.05）；MTHFR C677T与A1298C位点CC/AC、CT/AA、CT/AC、TT/AA、TT/AC组合基因儿童患CHD的风险分别为CC/AA组合基因的3.039、2.718、3.545、2.861、7.091倍（均P<0.05）；MTHFR C677T与G1793A位点TT/GG组合基因儿童患CHD的风险为CC/GG组合基因的2.551倍（χ²=7.133，P<0.05）；MTHFR A1298C与G1793A位点AC/GG组合基因儿童患CHD的风险为AA/GG组合基因的2.505倍（χ²=6.448，P=0.011）。结论 MTHFR C677T、A1298C突变是CHD发生的危险因素，MTHFR C677T与A1298C、MTHFR C677T与G1793A、MTHFR A1298C与G1793A组合基因对CHD的发生存在联合作用

Association of MTHFR gene polymorphism with congenital heart disease

Objective To investigate the association between polymorphism of methylenetetrahydrofolate reductase gene (MTHFR) and the risk of congenital heart disease (CHD) and to provide references for CHD control.Methods A hospital-based case-control study was conducted in 2012 among 150 children with simple CHD and 150 healthy children vistiting the same hospital for physical examination.The genotypes of MTHFR C677T,A1298C,G1793A of the participants were determined with polymerase chain reaction and restriction fragment length polymorphism analysis (PCR-RFLP) and analyzed.Results Compared with the wild CC genotype,the heterozygosity (CT) of MTHFR C677T is associated with the increased risk of CHD (odds ratio[OR]=2.249,95%confidence interval[95%CI]:1.305-3.877,P=0.003) and the homozygous mutant genotype (TT) is associated with the increased risk of CHD significantly (OR=3.121,95%CI:1.612-6.043,P=0.001);compared with the wild allete (C),the mutant allete (T) of MTHFR C677T is associated increased risk of CHD (OR=1.813,95%CI:1.310-2.508,P=0.000).Compared with wild AA genotype,the heterozygosity (AC) of MTHFR A1298C is associated with the increased the risk of CHD (OR=2.177,95%CI:1.183-4.077;P=0.011) and the mutant allete (C) is associated with the increased risk of CHD (OR=2.017,95%CI:1.128-3.604;P=0.016).No statistical differences in the frequencies of the heterozygote (GA) and homozygote (AA) and the mutant and wild allete of MTHFR G1793A were observed between the cases and the controls (P=0.145,P=0.158).There are joint effects of MTHFR C677T and MTHFR A1298C,MTHFR A1298C and MTHFR G1793A on the risk of CHD.Conclusion These findings suggest that genetic polymorphism in MTHFR C677T and MTHFR A1298C might contribute to the risk of CHD incidence and there are interactions for the effects of MTHFR C677T and MTHFR A1298C,MTHFR A1298C and MTHFR G1793A.