Association of CDKN2BAS gene polymorphism with periodontitis and Coronary Artery Disease from South Indian population

Background: Periodontal disease (PD), a chronic inflammatory disorder mediated by progressive destruction of the oral cavity is one of the key factors for many systemic disorders including Coronary Artery Disease (CAD). The upregulation of CDKN2BAS, a long noncoding RNA gene expression in gingival epithelial cells and gingival fibroblasts of periodontitis shows a strong correlation between the severity of atherosclerosis and PD. Considering the crucial role of CDKN2BAS gene polymorphisms (rs496892 G > A and rs7865618 A > G) and its expression the present study sought to identify the possible association with the disease predisposition in South Indian population. Methods: For the present case-control study a total of 200 subjects that include 100 PD-CAD patients and 100 controls were recruited with prior consent. Genomic DNA and RNA were extracted and utilized for genotyping via ARMS-PCR and PCR-RFLP, and expression using RT-PCR respectively. Results: The results showed a significant association of both the polymorphisms with that of the disease predisposition. The wild type genotypes (GG: OR-0.37; p-0.001; & AA: OR-0.29; p-0.005) conferred protection against the disease, whereas, the heterozygotes (GA: OR-2.45; p-0.004 & AG: OR-3.41; p-0.0001) conferred risk towards the disease, suggesting the involvement of the variant allele in disease causation. These results were further confirmed by haplotype analysis among A-G block (two variant alleles at both loci) with 2.5 fold risk (OR = 2.49, 95% CI = 1.16-5.36, p = 0.02) and G-G block (single risk allele at rs7865618 locus) with 3-fold risk (OR-3.0; p-0.01) towards the disease, suggesting the dominant involvement of rs7865618 in the disease causation. Though the expression of the CDKN2BAS gene is more in patients than controls, the variant genotypes among patients were evaluated to be down-regulated than the other genotypes. Conclusion: The present study concludes that the two selected polymorphisms have significant involvement individually and in interaction with each other in the disease predisposition. The expression studies also suggest that the selected polymorphisms in the 9p21.3 locus affect the CDKN2BAS gene expression. However, the results obtained in the present study should be confirmed with large samples in other ethnic cohorts.