MTHFR基因多态性与胎儿先天性心脏畸形的关系

Association of fetal congenital heart diseases with methylenetetrahydrofolate reductase gene polymorphisms

目的研究探讨怀有先天性心脏病胎儿的孕妇叶酸代谢通路基因的多态性,及其与先天性心脏病(congenital heart disease,CHD)易感性之间的关系。方法按照纳入标准收集产前诊断B超彩色多普勒心动图诊断先天性心脏病320例,抽取外周静脉血,采用PCR-RELP方法检测MTHFR677位点和MTHFR1298位点的基因多态性。结果 (1)基因位点多态性:对照组和病例组的C和T等位基因、A和C等位基因,2组差异均有统计学意义(χ~2=16. 589,P <0. 001;χ~2=5. 078,P=0. 020)。(2)基因型多态性:对照组和病例组的CC、CT、TT基因型,2组差异有统计学意义(χ~2=15. 282,P <0. 001),对照组和病例组的AA、AC、CC基因型2组差异无统计学意义(χ~2=5. 092,P=0. 080)。(3)分层研究中:在法洛四联症小组,病例组的CC、CT、TT基因型及AA、AC、CC基因型同对照组差异均存在统计学意义(χ~2=7. 794,P=0. 020;χ~2=8. 998,P=0. 010);在室间隔缺损小组,病例组的CC、CT、TT基因型同对照组差异存在统计学意义(χ~2=10. 407,P <0. 001),而AA、AC、CC基因型同对照组差异无统计学意义(χ~2=0. 667,P=0. 720)。结论母亲MTHFR C677T多态性与子代先心病发生相关,且分层研究中提示母亲MTHFR C677T多态性与子代法洛四联症、VSD发生相关。另研究结果示病例组和对照组MTHFR A1298C基因型虽然无明显差异,但等位基因A/C差异有统计学意义,提示等位基因A/C为子代发生CHD的一个危险因素。

Objective To investigate the polymorphism of folate metabolism pathway genes in pregnant women with congenital heart diseases（CHD） , and to explore the relationship between the gene polymorphisms and the susceptibility to CHD. Methods According to the inclusion criteria, Collected 320 cases of fetal congenital heart disease diagnosed by color Doppler echocardiography. From peripheral venous blood, PCR-RELP method was used to detect the polymorphism of MTHFR677 and MTHFR1298 loci. Results （1）Gene loci polymorphism： In the control group and CHD group, C and T allele,A and C alleles all have differences in the 2 groups was statistically significant（χ^2 = 16. 589, P 〈0. 001 ; χ^2 = 5.078, P =0. 020）; （2）Genotype polymorphism： In the control group and CHD group, CC, CT, TT genotype have differences in the both groups was statistically significant（ χ^2 = 15. 282, P 〈 0.001 ）. AA, AC and CC genotype have no statistically significant difference in 2 groups（ χ^2= 5. 092, P = 0. 080）; （3）In the study of stratified： Tetralogy of fallot group CC, CT and TT genotype and AA, AC and CC genotype, with the control group there were statistical significance （ χ^2 = 7. 794, P = 0. 020 ;χ^2 = 8. 998, P = 0. 010） ; Ventricular septal defect group CC, CT, TT genotype, with the con- trol group there were statistical significance（ χ^2= 10.407, P 〈 0.001 ） , And AA, AC and CC genotype, with the control group there were no statistical significance （ χ^2 = 0. 667, P = 0. 720）. Conclusion The MTHFR C677T polymorphism of mother is associated with congenital heart disease in children. Hierarchical research tips that the MTHFR C677T polymorphism of mother is associated with occurrence of tetra logy of fallot and ventricular septal defect in children. The other results in the case group and the control group MTHFR A1298C genotype although no obvious difference, bat the A/C allele is having the significant difference, prompt allele A/C to children is A risk factor of CHD.