From Genes to Gums: The Possible Potential Role of Vitamin D Receptor Polymorphisms in Periodontal Inflammatory Pathways

Objective: This study aimed to investigate the association between VDR gene variants (EcoRV[rs4516035], FokI [rs2228570], and Cdx2 [rs11568820]) and susceptibility to periodontitis, as well as their relationship with GCF cathelicidin levels.Methods: This is a prospective case-control study with 166 participants (82 cases and 84 controls), aged 20 to 45 years. Cases were selected from a tertiary hospital in Karachi, Pakistan. Periodontitis was diagnosed and staged according to the clinical indices, including Periodontal Disease Index [PDI], Oral Hygiene Index [OHI-S], and Gingival Bleeding Index. GCF was collected from standardised sites, and cathelicidin was quantified by ELISA. Serum vitamin D was measured by chemiluminescent immunoassay. Genotyping for VDR polymorphisms was performed by PCR–RFLP (EcoRV, FokI) and T-ARMS-PCR (Cdx2). Data was analysed using the SPSS 22.Results: The EcoRV AA genotype (p<0.001) (OR=13.776, 95% CI=5.791-32.768) and FokI Ff genotype (p<0.05) (OR=5.167, 95% CI=2.593-10.296) were significantly associated with increased risk of periodontitis. The EcoRV polymorphism also showed significant associations with OHI-S and PDI scores (p<0.05). GCF cathelicidin levels positively correlated with PDI (r=0.34, p=0.002).Conclusion: VDR polymorphisms, particularly EcoRV and FokI, appear to influence susceptibility to periodontitis and its clinical severity, while cathelicidin levels correlate with disease progression. These results underscore the association between vitamin D signalling and innate immune responses and bolster a genetic component to periodontal disease.