Validation of CDKN2A Variant rs10757278 in Pakistani Cardiomyopathy Patients

Abstract

Objectives: This study aimed to evaluate the association of the rs10757278 single nucleotide polymorphism (SNP) with cardiomyopathy, particularly its role in genetic susceptibility to ischemic dilated cardiomyopathy (IDCM). Methodology: A case-control study was conducted including 200 participants—100 cardiomyopathy patients and 100 healthy controls. Clinical and echocardiographic parameters were systematically recorded. Genotyping for rs10757278 was performed using tetra-primer ARMS-PCR. Allele and genotype frequencies were analyzed with odds ratios, and Hardy-Weinberg equilibrium was assessed to determine genetic association. Results: Logistic regression analysis revealed a significant association of rs10757278 with cardiomyopathy (Chi-square = 11.679, p = 0.00291) in both allelic and genotypic distributions. The GG genotype (p = 0.00958) conferred an increased risk, with the G allele identified as the risk allele. Among cardiomyopathy subtypes, IDCM showed a significant association with rs10757278, particularly with the GG and AG genotypes (p = 0.02613 and p = 0.00104, respectively). Logistic regression indicated that the G allele substantially increased IDCM risk (p = 0.0031, OR = 3.19, 95% CI = 1.51–7.17), while the A allele appeared protective (p = 0.00961, OR = 0.35, 95% CI = 0.15–0.77). This SNP, a known genome-wide association study (GWAS) hit, is strongly linked to coronary artery disease (CAD) and ischemic dilated cardiomyopathy, highlighting its potential as a biomarker for cardiomyopathy risk stratification. Conclusion: The rs10757278 variant is significantly associated with cardiomyopathies, particularly ischemic dilated cardiomyopathy, in the Pakistani population. The G allele serves as a genetic predictor of disease susceptibility. Larger, multi-center studies are warranted to validate these findings and facilitate early diagnosis and genetic risk profiling for cardiomyopathies.