Establishment of Relational Model of Congenital Heart Disease Markers and GO Functional Analysis of the Association between Its Serum Markers and Susceptibility Genes.
OBJECTIVE
The purpose of present study was to construct the best screening model of congenital heart disease serum markers and to provide reference for further prevention and treatment of the disease.


METHODS
Documents from 2006 to 2014 were collected and meta-analysis was used for screening susceptibility genes and serum markers closely related to the diagnosis of congenital heart disease. Data of serum markers were extracted from 80 congenital heart disease patients and 80 healthy controls, respectively, and then logistic regression analysis and support vector machine were utilized to establish prediction models of serum markers and Gene Ontology (GO) functional annotation.


RESULTS
Results showed that NKX2.5, GATA4, and FOG2 were susceptibility genes of congenital heart disease. CRP, BNP, and cTnI were risk factors of congenital heart disease (p < 0.05); cTnI, hs-CRP, BNP, and Lp(a) were significantly close to congenital heart disease (p < 0.01). ROC curve indicated that the accuracy rate of Lp(a) and cTnI, Lp(a) and BNP, and BNP and cTnI joint prediction was 93.4%, 87.1%, and 97.2%, respectively. But the detection accuracy rate of the markers' relational model established by support vector machine was only 85%. GO analysis suggested that NKX2.5, GATA4, and FOG2 were functionally related to Lp(a) and BNP.


CONCLUSIONS
The combined markers model of BNP and cTnI had the highest accuracy rate, providing a theoretical basis for the diagnosis of congenital heart disease.
Department of Cardiovascular Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou 450052, China; Department of Cardiovascular Medicine, Zhengzhou Central Hospital, Zhengzhou University, No. 195 Tongbai Road, Zhengzhou 450007, China.
Min
M
Liu
Department of Cardiovascular Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou 450052, China.
Luosha
L
Zhao
Department of Ultrasound Diagnosis, Directly under Hospital of Henan Military Region, No. 18 Jinshui Road, Zhengzhou 450000, China.
Jiaying
J
Yuan
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019295:Computational Biology / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000097:blood* / Q000175:diagnosis*; D000072576:Homeobox Protein Nkx-2.5 / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D020097:Natriuretic Peptide, Brain / Q000097:blood; D012372:ROC Curve; D012044:Regression Analysis; D015203:Reproducibility of Results; D012307:Risk Factors; D060388:Support Vector Machine; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
D015415:Biomarkers; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D000072576:Homeobox Protein Nkx-2.5; C095552:NKX2-5 protein, human; D014157:Transcription Factors; C117427:ZFPM2 protein, human; D020097:Natriuretic Peptide, Brain