Abstract
OBJECTIVES: The objective of this study was to investigate the association of methylenetetrahydrofolate reductase (MTHFRc.677C>T)and methionine synthase reductase (MTRR c.66A>G) genetic polymorphisms with the occurrence of congenital heart disease (CHD) and its subtypes in children. MATERIALS AND METHODS: This was a hospital-based case-control which included patients aged 0-11 months hospitalized between July 2022 and December 2023 with an echocardiographically confirmed CHD, and healthy age-matched controls recruited from the immunization clinic, after informed parental consent. Genotyping for MTHFRc.677C>Tand MTRR c.66A>Gwas performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A total of 245 cases (73 (29.8%) female infants) and 245 controls (77 (31.4%) female infants) were included. MTHFRc.677C>T(TT genotype, OR = 2.75, 95%CI: 1.6-4.5) and MTRR c.66A>G (GG genotype, OR = 2.62, 95%CI: 1.6-4.0) were associated with CHD. Subtype analysis showed a higher risk for ventricular septal defect (VSD) (OR = 5.67, 95%CI: 3.1-10.0 ), atrial septal defect (ASD) (OR = 9.51, 95%CI: 4.9-18.4), and patent ductus arteriosus (PDA) (OR=15.52, 95%CI: 7.1-33.7) for MTHFR c.677C>T, while MTRR c.66A>Gwas associated with ASD (OR = 8.67, 95%CI: 4.9-15.0) and PDA (OR = 18.54, 95%CI:9.3-36.9). The T allele of MTHFR c.677C>T and the G allele of MTRR c.66A>Gwere significantly more common in CHD cases (OR= 1.73, 95%CI: 1.3-2.2 and OR= 1.85, 95%CI: 1.4-2.3, respectively) compared to controls. CONCLUSION: MTHFRc.677C>Tand MTRR c.66A>Gpolymorphisms are associated with increased CHD risk, particularly in VSD, ASD, and PDA. The higher prevalence of T and G alleles in CHD cases suggests their potential role as genetic risk factors, emphasizing their relevance in CHD susceptibility and risk assessment.