The Association Between NKX2.5 And MTHFR Polymorphism Loci Of Congenital Heart Disease Related Genes And Adult Cardiovascular Disease

Objective: Explore the genetic susceptibility between Homobox transcription factor gene rs3729753、rs2277923 with Methylene Tetrahydrofolate Reductase gene rs1801131、rs1801133 single nucleotide polymorphisms and adult cardiovascular disease,as well as children congenital heart disease,also the correlation between genes.MTHFR related markers homocysteine in the course of forming cardiovascular disease clinical diagnostic value and relevance to the MTHFR gene.Methods: Use the qualitative theory of system evaluation and Quantitative methods of Meta analysis in evidence based medicine analysis the correlation between MTHFR gene C677 T polymorphism and cardiovascular disease.Empolying case-control study to collect sample,105 cases of normal control group and 108 cases of adults cardiovascular disease,53 cases of normal control group and 49 cases of childen congenital heart disease.Collecting general clinical information of the research object and detecting of serum homocysteine levels.Using polymerase chain reaction to amplificate NKX2.5 rs3729753 rs2277923 and MTHFR gene rs1801131 rs1801133 polymorphism loci fragment,generation of sequencing technology to detecting genotyping distribution of each point.Using chi-square test to analysis association between four polymorphism loci and risk of cardiovascular disease,as well as genotype combination of point analysis.Using one-way AVOVA the correlation of rs1801131 rs1801133 loci genotypes and serum Hcy levels.Logistic regression analysis of cardiovascular disease risk factors.Draw the ROC curve evaluation Hcy and various risk factors on the clinical value of diagnosing heart disease.Results: Evidence-based medicine Meta analysis showed in the following five genetic models merger analysis,there are MTHFR gene C677 T polymorphism and the significant correlation of cardiovascular disease: allele model(T vs C)[OR = 1.39,95% CI(1.17,1.17),P = 0.0002].The homozygous model(TT vs.CC)[OR = 1.57,95% CI(1.16,2.12),P = 0.003] Hybrid model(TC vs CC)[OR = 1.69,95% CI(1.26,2.27),P = 0.0004] The dominant genetic model(TT + TC vs CC)[OR = 1.53,95% CI(1.21,1.94),P = 0.0005] The implicit genetic model(TT vs.TC + CC)[OR = 1.37,95% CI(1.08,1.73),P = 0.01].Subgroup analysis showed higher morbidity risk in subgroups: the coronary group,the implicit genetic model [OR = 1.38,95% CI(1.17,1.62),and P = 0.0001] Myocardial infarction,the allele model [OR = 1.71,95% CI(1.37,2.13),P < 0.00001] Age < 50 age group,homozygous model [OR = 2.23,95% CI(1.58,3.17),P < 0.00001].Normal control group and cardiovascular diseases in TG,TC,HDL and LDL,LP(a),Hcy level was statistically difference(P < 0.05).In the normal control group and disease group in the distribution of genotype frequency,the unconditioned Logstic regression analysis,rs1801131,rs1801133,rs2277923 between the two groups was statistically significant(P < 0.05),rs3729753 no statistical significance between the two groups(P > 0.05).No found difference between each point in the different diseases rs1801131(chi-square = 5.799,P = 0.122),rs1801133(chi-square = 4.221,P= 4.221),rs2277923(chi-square = 1.154,P = 1.154).Single factor analysis of variance in genotype CC,serum level of Hcy in CT,TT(F = 17.231,P = 0.000)difference was statistically significant,the genotype AA,AC,serum level of Hcy in CC(F = 6.900,P = 0.001)difference was statistically significant.14 cardiovascular disease risk factors for Logistic regression analysis,correlation degree with the OR and 95% CI said,screen out nine factors: TG,TC,HDL and LDL,LP(a),Hcy,rs1801131,rs1801133,rs2277923;The linear correlation analysis: Hcy and negatively correlated with HDL,r = 0.217,P = 0.005,Hcy and LP(a)were positively correlated,r = 0.192,P = 0.015;ROC area under the receiver-operating curve of Hcy in the maximum is 0.950,it is the biggest value to the diagnosis of disease.Conclusion: Evidence-based medicine results show that the MTHFR gene C677 T polymorphism and the risk of developing cardiovascular disease has significant correlation,mutant allele T significantly increased the risk of cardiovascular disease.MTHFR gene rs1801131 loci allele C(AC,CC),rs1801133 loci allele T(CT,TT)and NKX2.5 gene rs2277923 loci allele A(GA,AA)associated with the risk of cardiovascular disease,can be used as the risk of disease factor to predict disease,also can estimate the severity of disease,and process.The MTHFR gene rs1801131 site AC,CC genotype and rs1801133 site CT,TT genotype are associated with high Hcy serum levels,and Hcy can be used as an effective helper factor to diagnose cardiovascular disease.Rs1801131,rs1801133,combination rs2277923 gene mutations are more likely than a single gene mutation to disease,have combined to the happening of the disease.