Study On Genetic Association Of Atrial Septal Defect Associated Pulmonary Arterial Hypertension

Objective:Based on this study related to pulmonary hypertension patients with atrial septal defects(genetic testing,whether related to pulmonary hypertension patients with atrial septal defects(containing always has a clear PAH gene mutation,so that the lack of related clinical know room pulmonary hypertension associated with genetic gene is,more conducive to early identification of intervention,and can improve the prognosis of patients.Methods:Peripheral venous blood samples were selected from 45 ASD-PAH patients diagnosed and admitted to the Affiliated Yan ’an Hospital of Kunming Medical University from January 2018 to December 2020,including 10 males and 35 females,aged 19-70 years.All the selected patients were confirmed as ASD-PAH patients by clinical physical examination,heart color ultrasound,right heart catheter and other related examinations,and were screened into the group.Venous blood was collected from all enrolled patients in the early morning and on an empty stomach.The relevant genomic DNA was extracted from the venous blood of the subjects,and whole-exome sequencing(WES)was carried out through the new generation of high-throughput sequencing(Illumina).After discarding the low-quality sequences,high-quality sequences were obtained.The data will then be compared with the genetic database using the relevant software.Evaluate the quality of the coverage of the target area.The screened genes were mutated into about 19 common known PAH pathogenic genes(BMPR2,EIF2AK4,TBX4,ATP13A3,GDF2,SOX17,AQP1,ALK1,Smad9,ENG,KCNK3,Cav1,Smad4,Smadl,KLF2,and BMPR1)B,KCNA5,BMP9,PTGIS,etc.).SPSS21.0 statistical software was used for data analysis,and the classification variables were expressed as percentages.The chi-square test was used to compare the classification variables between PAH-related pathogenic factors and pulmonary hypertension severity in ASD-PAH patients.The test was expressed as mean±standard deviation(mean±SD).P value<0.05 in the above analysis was considered statistically significant.Results:Out of a total of 45 ASD-PAH patients,mutations were found in 44 ASD-PAH patients,equivalent to 97.7%of all cases.After correlation analysis,we found that a total of 25 of 45 ASD-PAH patients(55.6%)were detected to carry a rare mutation in eIF2AK4.Among the other PAH pathogenic genes,10 cases(22.2%)of TBX4 gene mutation,4 cases(8.9%)of ENG gene mutation,2 cases(4.4%)of ALK1 gene mutation,2 cases(4.4%)of Smad1 gene mutation,and 1 case(2.2%)of KLF2 gene mutation were found,all of which were heterozygous mutations.No mutation was found in other genes.The eIF2AK4(c.1321A>C)gene mutation type was 21 cases(46.7%).Then,patients with and without PAH-related harmful mutations were compared,and it was found that compared with patients without PAH-related pathogenic gene mutations,patients with PAH-related pathogenic genes had higher mean pulmonary artery pressure and were more likely to lead to severe pulmonary hypertension,with statistical significance(P<0.01).Conclusion:1.Mutations in EIF2AK4,TBX4,ENG,ALK1,Smad1,BMPR2,and other genes may be an important pathogenic factor for the occurrence of pulmonary hypertension associated with atrial septal defect.2.Among patients with atrial septal defects associated with pulmonary hypertension,those with known PAH-related pathogenic gene mutations showed faster hemodynamic progression and more severe pulmonary hypertension.