The Relationship Between The Regional Polymorphism Of Methylenetetrahydrofolate Reductase Gene And Congenital Heart Disease In Children

IntroductionCongenital heart disease(CHD)threated to the life and health is one of the most common birth defects in infants and young children,which bring heavy burden to society and family.In recent years,great progress has been made in the etiology of congenital heart disease,congenital heart disease is not a single factor or the result of a simple addition,but the result of a combination of multiple risk factors.At present,it is believed that genetic factors and environmental factors(industrial and agricultural pollution,X-ray radiation,air pollution,smoking,alcohol abuse,infection during pregnancy,pregnancy medication,psychological factors during pregnancy and pregnancy disorders)are related to CHD.The researchers do not stop studying the etiology of CHD,and gene research continues to deepen,but still can not fully explain the reasons.Early detection of susceptibility genes associated with congenital heart disease,targeted to study its preventive measures,is helpful to clarify the etiology of CHD furtherly and reduce the incidence of congenital heart disease.Objective:To study the correlationship of Yimeng children of Han nationality in the methylenetetrahydrofolate reductase(MTHFR)C677T gene polymorphism and susceptibility to congenital heart disease(CHD),investigate the distribution of MTHFR genotypes in this area and the blood homocysteine levels,explore the relationship between gene mutation and the pathogenesis of congenital heart disease,provide a reference for the etiology and prevention of congenital heart disease.Methods:From Octorber 2014 to June 2016,at Linyi City People's hospital,the children who suffered from congenital heart disease 110 cases were choosed as case group(CHD group),and selected physical examination of 110 healthy children as control group,the two group of age is 1-5 years old,average 3,2 years old,gender,age had no statistical difference.Comparative study in the two groups,the method of restriction fragment length polymorphism analysis of polymerase chain reaction(PCR-RFLP)was used.The MTHFR gene C677T polymorphism of the two groups were divided into different genotypes,the two groups of the genotypes frequency and distribution were contrasted.Plasma homocysteine level was determined by ELISA and correlation analysis of C677T gene polymorphism and congenital heart disease susceptibility and plasma homocysteine levels were conducted respectively.Results:The MTHFR gene has 3 genotypes CC?CT and TT in the 677 position,T was mutant allele;the CHD group and control group MTHFR gene C677T genotype frequencies of CC,CT,TT were 0.109,0.382,0.509 and 0.50,0.409,0.091,respectively.There were significant differences between the two groups(?2=59.796,P= 0.000),CHD group with T genotype frequency was significantly higher than CC genotype frequency;as the MTHFR gene C677T allele,C?T frequencies were 0.30,0.70 and 0.705,0.295 respectively,the difference was statistically significant between the two groups(?2=72.011,P=0.000).CHD group allele gene frequency of T was higher than the control group C allele frequency.Carrying the mutant T allele genotype of individuals at risk for congenital heart disease is about5.6 times of carrying the wild-type allele of the C genotype(95%CI3.697?8.373,P=0.000).Compared with the CC genotype homozygous,heterozygous CT genotype had higher risk of congenital heart disease(OR=4.208,95%CI2.015?9.082,P=0.000);Homozygous TT genotype individuals at risk for congenital heart disease is 25.667 times higher than the wild type homozygote CC genotype(95%CI 10.249?64.276,P=0.000),TT homozygote for congenital heart disease risk is higher.Compared with the control group,plasma homocysteine levels is higher in the congenital heart disease group(15.35±1.02 vs 5.26±0.98),the correlation ship between MTHFR gene polymorphism and plasma homocysteine level was proved,the Spearman correlation coefficient was 0.502.Conclusion:Children with congenital heart disease in Yimeng Han nationality and healthy children,the distribution of allele frequencies and genotype of MTHFR 677 had statistical differences(P<0.05).The genotype frequency and gene frequency was higher in children with congenital heart disease who with T allele;mutant T allele was associated with increased susceptibility to CHD,the risk of mutant individuals who was homozygous TT genotype suffered congenital heart disease increased significantly;in the plasma of children with congenital heart disease,homocysteine levels in the area were significantly higher than those of healthy group,with the increased of T genotype proportion,plasma homocysteine increased correspondly.MTHFR gene C677T polymorphism is one risk of the factors which can lead to congenital heart disease happened in the children of Han nationality in Yimeng area.