The Association Between Angiotensin Converting Enzyme 2 Gene Polymorphism And Pulmonary Artery Hypertension Due To Congenital Heart Disease In Chinese Han

BackgroundCongenital heart disease(CHD)was one of the most common congenital malformations in Guangdong and worldwide.As one of the most serious complication of CHD,pulmonary artery hypertension(PAH)is diverse in its occurrence,progression,reaction to therapy and the prognosis.Early identify and intervention is a popular topic of CHD.Angiotensin converting enzyme 2(ACE2),as the homologous isomers of angiotensin converting enzyme,was able to counteract renin-angiotensin-aldosterone system and was proved to have protective effect on many cardiovascular diseases,including PAH.Moreover,the polymorphism of gene ACE2 was claimed to have relationship with occurrence and prognosis of several cardiovascular diseases.However,whether the polymorphism of gene ACE2 also affect PAH due to CHD(CHD-PAH)remain unclear.We conducted this study to investigate the relationship between single nucleotide polymorphism(SNP)of gene ACE2 and CHD-PAH in Chinese Han population.Method157 CHD-PAH patients and 223 CHD patients with normal pulmonary artery pressure received right heart catheterization and gene sequencing of ACE2 rs2074192,rs2285666 and rs2106809.The sequencing method was ligase detection reaction.Proportions were compared using chi-square test.Laboratory test results and hemodynamic parameters were compared using Mann-Whitney U test and Kruskal Wallis test.ResultOn the aspect of single genotype or allele,we did not find relationship between gene ACE2 SNPs and CHD-PAH.But female patients with heterozygous genotype had worse pulmonary circulation hemodynamic compared with homozygote.Among them,pulmonary output(PO),pulmonary index(PI)and ratio of pulmonary blood flow quantity to systemic blood flow quantity(Qp:Qs)in rs2074192 and Qp:Qs in rs2285666 were statistically different(p<0.05).Moreover,we found female CHD patients with C-C-A haplotype(rs2074192-rs2285666-rs2106809)had a higher risk to develop PAH(X2=5.07,P=0.02,OR=1,38,95%CI:1.03-1.84).Additionally,part of the pulmonary circulation hemodynamic in female patient with C-C-A>C-C-G?C-T-A?T-T-A and T-T-G haplotype was significantly worse than those without(P<0.05).Among all the comparison between different genetic grouping,no statistical difference was found in the laboratory test results and systemic circulation hemodynamic parameters.ConclusionWe find ACE2 SNPs was related with pulmonary circulation hemodynamic in female patients,and female CHD patients with C-C-A haplotype had 1.38-time higher risk of PAH.Gene ACE2 might perform in the co-dominance model.