The Study Of The Levels Of Blood MicroRNA In Patients Of Congenital Heart Disease With Pulmonary Hypertension

Objective:To detect the expression level of relevant miRNAs in blood of Congenital Heart Disease(CHD) combined with pulmonary hypertension(PH) patients,and investigated the correlation of those with pulmonary hypertension for the further study of diagnosis and treatment of PH.Methods:78patients with Congenital Heart Disease and20normal control patients were collected in the Yan’an hospital during eight month. The patients with congenital heart disease were divided into37cases of non-pulmonary arterial hypertension group,25cases of mild to moderate pulmonary arterial hypertension,and16cases of severe pulmonary arterial hypertension.The level of miRNAs in blood was detected by using real-time fluoresecnt quantitative PCR (Taqman probe), Choose RNU6B as endogenous control. Detect the expression level of miR-18a, miR-27b, miR-130a, miR-204in blood and investigated the correlation between miRNA and PH. Statistical analysis was performed by using SPSS17.0software.α=0.05was regarded as the statistical criterion. The linear correlation analysis was used for the correlation between the two factors. The diagnostic value of different variables was judged by the ROC curves.Results:1. The expression level of miR-18a, miR-27b, miR-130a and miR-204in blood were different in the group A (normal control group), group B (Congenital Heart Disease with non-pulmonary arterial hypertension group), group C (Congenital Heart Disease with mild to moderate pulmonary arterial hypertension group) and group D (Congenital Heart Disease with severe pulmonary arterial hypertension group)(P<0.05). 2. Compared with group A, the levels of miR-18a and miR-130in group D,group C and group B were significant high expression (P<0.001).Compared with group B, the levels of miR-18a and miR-130in group D and group C were significant high expression (P<0.001).Compared with group C, the levels of miR-18a and miR-130in group D was significant high expression (P<0.001).3. Compared with group A, the levels of miR-27b in group D and group C was significant high expression (P<0.001), but there is no significant difference in group B(P>0.05). Compared with group B, the levels of miR-27b in group D and group C were significant high expression (P<0.001).Compared with group C, the levels of miR-27b in group D was significant high expression (P<0.001).4. Compared with group A, the levels of miR-204in group D, group C and group B were significant low expression(P<0.001).Compared with group B, the levels of miR-204in group D and group C were significant low expression (P<0.001).Compared with group C, the levels of miR-204in group D was significant low expression(P<0.001).5. Through correlation and regression analysis,there was a significant positive correlation between Pulmonary arterial pressure and miRNAs (miR-18a, miR-27b, miR-130a)(r=0.927, r=0.927, r=0.933,P<0.001).There was a significant negative correlation between Pulmonary arterial pressure and miR-204(r=-0.773,P<0.001).6. When the expression level of miR-18a, miR-27b, miR-130a and miR-204in blood were considered as the diagnostic markers, the area under ROS curve of which were respectively0.921(95%CI,0.861～0.981, P<0.001)、0.943(95%CI,0.902～0.984, P<0.001)、0.955(95%CI,0.916～0.994, P<0.001)、0.898(95%CI,0.839～0.956, P<0.001)Conclusions:1.The expression level of miR-18a, miR-27b and miR-130a in the patients with Congenital Heart Disease combined with pulmonary hypertension have significantly increased according pulmonary arterial pressure increased. However,the expression level of miR-204was significantly declined according pulmonary arterial pressure increased. 2.There was a significant positive correlation between Pulmonary arterial pressure and miRNAs (miR-18a, miR-27b, miR-130a) which of the patients with Congenital Heart Disease combined with pulmonary hypertension, conversely, there was a negative correlation between Pulmonary arterial pressure and miR-204.3.The expression levels of miR-18a, miR-27b and miR-130a and miR-204can be used as the good clinical serological indexes for diagnosis of Congenital Heart Disease combined with pulmonary hypertension.4.There are miRNAs in human blood, which can be detected conveniently by real-time fluoresecnt quantitative PCR method. Taqman probe is a sensitive,specific and convenient method to detect miRNA quantitatively.