DefinePK

Abstract

Background: Genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) genes have been linked to the pathogenesis of congenital heart defects (CHDs). However, their precise role in CHD susceptibility remains to be fully elucidated. Aim: This study aimed to evaluate the association of eNOS (rs1799983) and ACE (rs4646994) gene polymorphisms with the risk of CHDs in an Indian population. Methods:A case-control study was conducted involving 112 children with CHDs and 112 age-matched healthy controls. Genomic DNA was extracted from peripheral blood, and genotyping was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Results were confirmed by Sanger sequencing.
Results: For eNOS (rs1799983), both the GT genotype P < 0.0001; OR = 4.7435 (2.5849 to 8.7050) and GG genotype P = 0.0051; OR = 3.3281 (1.4350 to 7.7189) were significantly associated with increased CHD risk. The dominant model (GT + GG) also showed a strong association P < 0.0001; OR = 4.3293 (2.4679 to 7.5945) For ACE (rs4646994), the ID genotype resulted in P= 0.0307; OR= 2.3824 (1.0841 to 5.2352) DD genotype was significantly more frequent among CHD cases P < 0.0001; OR = 5.2941(2.8342 to 9.8892) while the dominant model (ID/DD) demonstrated a strong association with CHD risk P < 0.0001; OR = 4.1294 (2.3629 to 7.2166). Allele frequency analysis revealed a significantly higher frequency of the G allele in  eNOS (rs1799983) and D allele ACE (rs4646994) among cases compared to controls (both P < 0.0001), suggesting their roles as potential genetic risk factors for CHD.
Conclusion: Polymorphisms in eNOS (rs1799983) and ACE (rs4646994) genes are significantly associated with increased susceptibility to congenital heart defects in the studied Indian cohort. These findings provide valuable insight into the genetic basis of CHDs and support the potential for using these markers in genetic screening and risk assessment.