Vitamin D Binding Protein and Receptor Prevalence in a Large Population with Periodontitis: Genetic Polymorphisms and Transcriptomic Profiling

Abstract

Background: There is an ongoing controversy regarding the expression of vitamin D receptor (VDR) and binding protein (VDBP) genes, as well as their polymorphisms, in periodontitis. We examined eight single nucleotide polymorphisms (SNPs) and performed a transcriptome-level bioinformatics analysis to clarify their relationship with periodontitis. Methods: To explore VDR and VDBP polymorphisms, 600 subjects were included, including 307 patients with chronic periodontitis (CP) and 293 healthy controls. Genomic DNA was extracted from peripheral venous blood collected from each subject. A MassARRAY system was used to detect genetic polymorphisms, including rs1544410G/A (BsmI), rs2228570C/T (FokI), rs7975232G/T (ApaI), rs731236T/C (TaqI), rs739837G/T, rs9729G/T, and rs3847987C/Ain the VDR gene, and rs7041A/C in the VDBP gene. Then, we analyzed transcriptome sequencing datas of gingival tissues from two single-cell transcriptome sequencing studies to identify differential expression profiles. The objective was to further explore the potential association between VDR gene and gingival tissues in individuals with chronic periodontitis (CP). Results: The regression analysis model revealed a significant relationship between rs739837G/T (P = 0.044) and rs7041A/C (P = 0.032) polymorphisms and CP susceptibility. Subjects carrying the TT genotype of rs739837showed a decreased risk of developing CP compared to those carrying the GG+GTgenotype (OR = 0.53, 95% CI = 0.29–0.99). Individuals carrying the AC+CC genotype of rs7041 showed a reduced risk of developing CP compared to those with the AA genotype (OR = 0.70, 95% CI = 0.51–0.97). Furthermore, allele C of rs7041was found to have a protective effect against periodontitis (P = 0.033, OR = 0.7525, CI = 0.5793–0.9776). However, no association was found between CP susceptibility and six other 6 SNPs (rs1544410, rs2228570, rs7975232, rs9729, rs731236, and rs3847987). Differential levels of VDR transcription were observed in gingival tissues during CP. Conclusions: VDR genetic variability and transcriptional expression are significant factors affecting susceptibility to CP. These findings suggested that rs739837 TT in VDR and rs7041 A/C in VDBP may be protective against periodontitis.