Vitamin D plays a crucial role in regulating calcium balance and promoting healthy bone formation within the endocrine system;however, the global population is facing a widespread issue of vitamin D deficiency[20]. Studies have shown that vitamin D deficiency may be an important factor contributing to periodontal disease, leading to an increased risk of periodontitis and aggravating the inflammatory response. Moderate vitamin D supplementation reduces periodontitis [21,22,23]. Vitamin D content and activity in the body are closely related to the functions of VDR and VDBP, which are important mediators of vitamin D that regulate bone metabolism and play a role in immunity [24].
The human VDR gene is located on chromosome 12 and is localized to 12q1. Its most prevalent single-nucleotide polymorphisms are BsmI, FokI, ApaI, and TaqI [16]. The VDBP SNPs are mostly found in rs7041, located on exon 11 [25]. In this study, the association between VDR (BsmI, FokI, ApaI, TaqI, rs739837, rs9729, and rs3847987) and VDBP (rs7041) SNPs in a Chinese population with or without CP was investigated. In the present study, a Han Chinese population in the northwest region of China was selected, and the influence of age and ethnic groups was controlled as far as possible for greater generalizability.
Studies on the association between VDR gene polymorphisms and CP mainly focused on BsmI, FokI, ApaI, and TaqI. Some studies have shown a significant association between polymorphisms and CP [11,16,26,27,28]. According to a meta-analysis conducted on the Chinese population [29], individuals with the AA+AG genotype of the VDR BsmI polymorphism were found to be more prone to periodontitis in southern China, whereas those with the ApaI TT+TG genotype had a lower risk of developing periodontitis in northern China. In the present study, no significant correlation was found between VDR gene polymorphisms BsmI, FokI, ApaI, and TaqI and the risk of CP based on allele frequencies or any genetic model in northern China, which is consistent with some other studies, including a meta-analysis [12, 30, 31, 32]. However, the conclusions of relevant studies are inconsistent, which may be the result of study population compositions, including differences in race, age, oral health status, or ethnic groups. Determining their precise relationship between these specific VDR alleles and CP requires further study.
The VDR alleles rs739837, rs9729, and rs3847987 have been identified as being linked to an increased risk of developing diabetes, lung cancer, and dental caries [33,34,35,36]. To our knowledge, this study represents the first report investigating the potential association between VDR alleles rs739837, rs9729, and rs3847987 and susceptibility to CP. Interestingly, we found that the rs739837 polymorphism was associated with CP in a recessive model, and subjects carrying the TT genotype of rs739837 had a lower risk of CP than those with the GG+GT genotype (OR = 0.53, 95% CI = 0.29–0.99). Therefore, the rs739837 polymorphism may affect susceptibility to CP in our population; however, whether it can be used as a susceptibility marker requires validation studies in a larger study population.
There is currently a lack of research examining the relationship between the VDBP rs7041 gene polymorphism and risk of developing periodontitis [37,38]. In 2016, Song et al. [39] examined VDBP gene polymorphisms (rs17467825, rs4588, rs7401) and risk of generalized aggressive periodontitis among a Chinese population. The study revealed a significant association between the rs17467825 GG genotype and the risk of the disease, whereas no significant association was observed for rs7401. In 2019, Bahareh et al. [40] discovered a novel association between VDBP gene polymorphisms (rs7401, rs4588) and chronic periodontitis (CP) in an Iranian population, marking the first instance of such a relationship being reported. Their study found a significant association between haplotypes of these two genes and susceptibility to severe CP. However, the small sample size due to stratification was a limitation of this study. Based on the currently available literature, our present study is the first to analyze the potential association between VDBP (rs7041) gene polymorphisms and CP in a Chinese population. We found that the rs7401 polymorphism was associated with CP under a recessive model, and subjects with the AC+CC genotype also had a lower risk of CP than those with the AA genotype (OR = 0.70, 95% CI = 0.51–0.97). Furthermore, allele C was found to protect against periodontitis in rs7041 individuals (OR = 0.7525, 95% CI = 0.5793–0.9776).
VDR is known to protect against inflammation by inhibiting the production of pro-inflammatory cytokines and promoting the production of anti-inflammatory cytokines. Numerous studies have shown that it inhibits the NF-κB pathway, which is induced by tumor necrosis factor-alpha (TNF-α) or lipopolysaccharide (LPS) in response to inflammation [41,42]. VDBP is a carrier protein responsible for transporting vitamin D. It affects inflammatory status by binding to certain inflammatory molecules such as LPS or bacterial DNAs, helping to neutralize their pro-inflammatory effects [43,44]. The association between the VDR (FokI) genotype and susceptibility to CP may reflect enhanced kappa B ligand (RANKL) expression, as previously demonstrated by knockdown of VDR using siRNA in human periodontal ligament (hPDL) cells [45].
In our study, we observed that the TT genotype of VDR rs739837 was associated with a decreased risk of CP compared to the GG+GT genotype of the same allele, indicating that the frequency of the TT genotype in periodontitis-susceptible patients is lower. Further analysis of VDR and gingival tissues in patients with CP revealed a significant positive correlation between VDR expression in fibroblasts and CP. There appears to be a connection between these two results. Specifically, in a study of hPDL fibroblasts and VDR, Erika et al. found that increased physiological concentrations of 25(OH)D3 regulated decreased VDR mRNA expression associated with the TT genotype of rs739837 [46]. Therefore, an increase in 25(OH)D3 levels in hPDL fibroblasts may lead to a decrease in the TT genotype of the VDR polymorphism rs739837, thereby increasing a person's susceptibility to periodontitis. Modulating mRNA expression levels to influence SNP expression may, at least in part, explain susceptibility to periodontitis.