Study of some biochemical and genetic markers in patients with congenital heart defects undergoing surgical correction: A case-control study

Objective: Congenital heart defects (CHDs) represent structural malformations of the heart that appear at birth and impair its function.In nearly half of CHD cases, the precise pathogenic mechanisms remain unknown due to the complexity of their etiology.Nevertheless, multiple genetic determinants have been identified as contributors to CHD development.This study aimed to evaluate the possible associations of circulating biochemical markers (cardiolipin and NADPH oxidase 2, NOX2) and genetic profile of three single nucleotide polymorphisms (SNPs) in lysocardiolipin acyltransferase, bone morphogenetic protein 4 (BMP4), and NOX2 genes in CHD patients undergoing surgical correction and correlate them with clinical outcomes.Methods: A case-control study was performed on 60 CHD patients (15 each with atrial septal defect, ventricular septal defect, patent ductus arteriosus and tetralogy of Fallot) and 40 healthy controls.Clinical data and echocardiography of all participants were collected.Serum levels of cardiolipin and Nox2 were detected utilizing high performance liquid chromatography "HPLC" and ELISA techniques respectively.BMP4 rs762642, LCLAT1 rs74357219, and cytochrome b-245 beta chain "CYBB" rs190924506 SNPs were analyzed via TaqMan TM assays and real-time PCR.Results: CHD patients exhibited significantly lower cardiolipin (145 vs. 764.5 mg/dL, p<0.001) and Nox2 (0.04 vs. 0.09 mol/L, p<0.001) compared to controls.Genetic analysis revealed dominance of AC genotype of BMP4 rs762642 SNP in CHD patients (83.3% vs. 10% in controls) and C-allele (50% vs. 15% in controls), p<0.001.The C-allele is regarded as a genetic risk factor for CHD with OR=0.333, 95%CI=0.179-0.620.There were higher frequency of TT genotype of LCLAT1 rs74357219 SNP (31.7% vs. 10%, p=0.014) and CT genotype of CYBB rs190924506 SNP (20% vs. 60%, p<0.001) in CHD patients relative to the controls with insignificant differences regarding their alleles frequencies.Postoperative complications included heart block (25%) and chest infection (10%).Cardiolipin and Nox2 correlated negatively with operation time, blood loss, and intensive care unit stay (p<0.05).Conclusion: Reduced cardiolipin and NOX2 levels, along with BMP4, LCLAT1, and CYBB polymorphisms, are significantly associated with CHD and postoperative outcomes.