Validation of GWAS-Identified CDKN2A Variant rs10757278 in Cardiomyopathy Patients of Pakistani Cohort

Cardiomyopathies, a leading cause of heart failure and mortality worldwide, are a diverse group of heart muscle disorders, with dilated cardiomyopathy being the most prevalent subtype. Numerous genetic variants, identified through GWAS and candidate gene studies, are associated with cardiomyopathies. This study aimed to evaluate the association of the rs10757278 SNP polymorphism on chromosome 9p21.3 near the CDKN2A and CDKN2B genes with cardiomyopathy, focusing on its role in genetic susceptibility to ischemic dilated cardiomyopathy. Methods: A case-control study was conducted with 200 participants (100 cardiomyopathy patients and 100 controls). Clinical and echocardiographic parameters were recorded, and genotyping was performed using tetra-arms PCR. Results: Statistical analysis revealed that rs10757278 was significantly associated with cardiomyopathy (Chi-sq=11.679, p=0.00291) in allelic and genotypic distributions. The GG genotype (p=0.00958) increased risk, identifying the G allele as the risk allele. For IDCM, significant associations were observed for GG and AG genotypes (p=0.02613, p=0.00104), with the G allele increasing risk (p=0.0031, OR=3.19, CI=1.51–7.17) and the A allele offering protection (p=0.00961, OR=0.35, CI=0.15–0.177). Conclusion: These findings highlight rs10757278 as a potential biomarker for cardiomyopathy risk profiling. Further large-scale studies are warranted to confirm these results and improve early diagnosis and genetic risk prediction for cardiomyopathies.