Association of the RBFOX1 rs6500744 Polymorphism with Periodontal Disease Severity in Adults with Obesity: A...

Obesity and periodontitis are chronic diseases that share inflammatory and metabolic pathways. The RBFOX1 gene was selected as an exploratory candidate gene because it encodes an RNA-binding splicing regulator, has been implicated in obesity-related phenotypes, and has been reported in candidate-gene analyses of periodontitis/metabolic traits. This study investigated the association between obesity, periodontal disease severity, and RBFOX1 rs6500744 polymorphism. This case-control study enrolled 106 adults: 53 with obesity (BMI ≥ 30 kg/m²) and 53 normoweight controls. Clinical and radiographic periodontal assessments determined disease severity, complexity, staging, and grading. Genotyping of the RBFOX1 rs6500744 polymorphism (CC, CT, TT) was performed using the TaqMan^® SNP Genotyping Assay and the 7500 Fast Dx Real-Time PCR system. Multivariable models adjusted for age, sex, smoking status, and clinically confirmed type 2 diabetes. Participants with obesity showed higher levels of periodontal disease than normoweight controls, indicated by greater pocket depths, attachment loss, and bone loss. Advanced stage (Stage III/IV; p = 5.35 × 10^-6) and Grade C periodontitis (p = 2.08 × 10^-7) were significantly more frequent in the obese group. The rs6500744 T allele was more common among individuals with obesity (46.2% vs. 30.2%; OR 1.99, p = 0.023). Periodontal damage appeared to increase progressively from CC to CT to TT genotype, but genotype-stratified estimates, particularly for TT homozygotes, were interpreted cautiously because of the small subgroup size and multiple testing. Both obesity and the number of T alleles were associated with increased periodontal severity in adjusted statistical models. VIFs were low, residual diagnostics did not indicate major assumption violations, smoking-stratified sensitivity analyses were directionally consistent, and the obesity × T-allele interaction was not statistically significant. Obesity is associated with more severe and extensive periodontal disease in this exploratory case-control cohort; however, residual confounding from significant smoking imbalances between groups cannot be excluded. The RBFOX1 rs6500744 T allele may mark increased susceptibility to periodontal tissue destruction, but the findings do not establish causality or clinical prognostic utility and require longitudinal validation in larger, ancestry-controlled populations.