MTHFRC677T基因多态性及血浆Hcy水平与胎儿先天性心脏病的关系

Analysis on the correlation between MTHFR C677T polymorphisms,homocysteine level and fetal congenital heart disease

目的探讨叶酸代谢关键酶亚甲基四氢叶酸还原酶(MTHFR) C677T基因多态性及血浆同型半胱氨酸水平与胎儿先天性心脏病(先心病)的关系。方法选取2016年8月-2018年2月于郑州大学第三附属医院就诊并定期产检的单胎健康孕妇作为研究对象,分为病例组(60例合并胎儿先心病的孕妇)和对照组(120例无胎儿先心病的孕妇),通过询问孕前及孕期补充叶酸情况,并采取孕妇口腔黏膜测定叶酸代谢酶MTHFRC677T基因型及测定孕早期血浆中同型半胱氨酸浓度,分别比较MTHFRC677T不同基因型及血浆中同型半胱氨酸与胎儿先心病的相关关系。结果 MTHFRC677T基因多态性与胎儿先心病有关。胎儿先心病组中纯合突变TT基因型频率高于对照组,差异具有统计学意义(χ2=9. 4,P=0. 002);对照组野生型CC基因型频率高于先心病组,差异具有统计学意义(χ2=9. 97,P=0. 002);先心病组T等位基因频率高于对照组,差异具有统计学意义(χ2=15. 7,P <0. 05)。与纯合子CC基因型相比,突变杂合子CT基因型及突变纯合子TT基因型合并先心病的风险分别是野生纯合子CC基因型患先心病风险的2. 541倍(95%CI:1. 113～5. 803,P=0. 024)与5倍(OR=3. 333,95%CI:2. 133～12. 960,P=0. 000);含T基因型(CT+TT)合并先心病的风险较高(OR=5. 257,95%CI:1. 542～7. 206);突变等位基因T合并先心病的风险约是野生型等位基因C合并先心病风险的2. 5倍(OR=2. 455,95%CI:1. 567～3. 847,P=0. 000)。CT基因型及TT基因型组中,其血Hcy水平均高于基因型为CC,且差异均具有统计学意义(P <0. 01)。TT基因型组中血Hcy水平高于CT基因型组中,差异具有统计学意义(P <0. 01)。先心病组中平均血Hcy(7. 12±1. 47)μmol/L,高于对照组平均血Hcy(6. 0±1. 11)μmol/L水平,两组比较差异具有统计学意义(P <0. 01)。结论叶酸代谢关键酶基因MTHFR基因多态性对胎儿先心病的发生有重要影响,是胎儿先心病发生的遗传易感因素,携带突变等位基因会增加血Hcy水平,进而增加胎儿先心病的风险。

Objective To assess the relationship between the MTHFR 677 TT genotype,homocysteine( Hcy) level and the risk of fetal congenital heart disease( CHD). Methods From June 2013 to August 2016,160 healthy pregnant women( single pregnancy)receiving regular prenatal examination in Henan Maternal and Child Health Care Hospital were selected and divided into case group( 60 pregnant women with CHD fetuses) and control group( 120 pregnant women with normal fetuses). Both the groups were asked about the folic acid supplementation before and during pregnancy. The genotype of folate metabolizing enzyme MTHFRC677 T in oral mucosa and the concentration of homocysteine in plasma were measured. The relationship between different genotypes of MTHFRC677 T and plasma homocysteine and fetal congenital heart disease was compared. Results MTHFRC677 T gene polymorphism was associated with fetal congenital heart disease. The genotype of MTHFRTT in CHD group was higher than that in control group(χ^2= 9. 4,P = 0. 002).The genotype of MTHFRCC in control group was higher than that in CHD group(χ^2= 9. 97,P = 0. 002). The frequency of T allele in CHD group was higher than that in control group(χ^2= 15. 7,P < 0. 05). Compared with homozygous CC genotype,the risk of CHD in homozygous CT genotype and in TT genotype were 2. 541 times( 95% CI: 1. 113-5. 803,P = 0. 024) and 5 times( OR = 5. 257,95%CI: 2. 133-12. 960,P = 0. 000) higher than that in homozygous CC genotype( 95% CI: 1. 113-5. 803,P = 0. 024);the risk of CHD in both CT and TT genotype was higher( OR = 5. 257,95% CI: 1. 542-7. 206). The risk of T gene mutation associated with CHD is about 2. 5 times higher than that of wild type allele C gene mutation associated with CHD.( OR = 2. 455,95% CI: 1. 567-3. 847,P =0. 000). In CT genotype and TT genotype group,the level of Hcy in blood was higher than that of CC genotype,and the difference was statistically significant. The blood Hcy level in the TT genotype group was higher than that in the CT genotype group,and the difference was statistically significant. The average blood Hcy7. 12 + 1. 47 umol/L in CHD group was higher than that in control group,and the difference was statistically significant( P < 0. 01). Conclusion MTHFR gene polymorphism,a key enzyme in folate metabolism,has an important effect on the occurrence of fetal congenital heart disease and is a genetic predisposing factor for the occurrence of fetal congenital heart disease,and Carrying mutation allele will increase blood Hcy level and increase the risk of fetal congenital heart disease.