Preliminary investigation on the molecular mechanisms underlying the correlation between VDR-FokI genotype and periodontitis.

The only polymorphism that could change the protein structure in vitamin D receptor (VDR) is the FokI polymorphism (rs2228570). The FF genotype has the strongest transcriptional activity of VDR and is correlated with higher susceptibility to periodontitis. To reveal the possible molecular mechanisms for the correlation preliminarily, the influence of VDR-FokI genotype on the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) in human gingival fibroblasts (hGFs) and human periodontal ligament cells (hPDLCs) was investigated in this study. hGFs and hPDLCs from 15 donors (five FF, seven Ff, and three ff) were treated with 1,25OH2 D3 , with or without the specific knockdown of VDR using siRNA. The mRNA and protein expression of OPG and RANKL were detected using real-time PCR and enzyme-linked immunosorbent assay, respectively. Both in hGFs and hPDLCs, 1,25OH2 D3 could significantly induce the mRNA and protein expression of RANKL, and FF genotype had significantly higher induction than the other genotypes, however, neither 1,25OH2 D3 nor VDR-FokI had significant influence on the OPG expression. As a result, the RANKL/OPG ratio was significantly elevated under 1,25OH2 D3 stimulation and FF genotype had the most remarkable elevation. When VDR was knocked down, all the differences among the three genotypes disappeared. The strongest transcriptional activity of FF genotype might contribute to the strongest enhancement of RANKL expression and RANKL/OPG ratio in hGFs and hPDLCs stimulated by 1,25OH2 D3 , which might help to reveal the mechanisms of the correlation between FF genotype and susceptibility to periodontitis.

Liu K ，Han B ，Hou J ，Meng H ... -  《-》

Influence of rs2228570 on Transcriptional Activation by the Vitamin D Receptor in Human Gingival Fibroblasts and Periodontal Ligament Cells.

Liu K ，Han B ，Meng H ，Hou J ... -  《-》

[Influence of vitamin D receptor FokI polymorphism on expression of CYP24A1 in periodontal cells].

Liu KN ，Meng HX ，Hou JX 《-》

VDR FokI polymorphism is associated with a reduced T-helper cell population under vitamin D stimulation in type 1 diabetes patients.

Type 1 diabetes (T1D) is an autoimmune disease mediated by T-helper (Th) cells. Additionally, the immune system regulator vitamin D, exerts its modulatory effects through the vitamin D receptor (VDR) expressed in Th cells. Furthermore, several genetic variants in the VDR gene including the VDR FokI (rs10735810) polymorphism have been implicated in T1D susceptibility in some Caucasian populations. Aim of the present study was to investigate the possible functional role of the VDR FokI gene polymorphism in Th cells from T1D patients and healthy controls (HC). Isolated Th cells from 23 HC and 20 T1D patients were stimulated for 72h with 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). After in vitro culture CD3(+)CD4(+) (CD4(+)) Th cell subsets were characterized by flow cytometry and gene expression of VDR was measured by Taqman assay. Finally, the VDR FokI polymorphism was genotyped. Significant lower VDR gene expression was observed in non-stimulated and 25(OH)D3 stimulated Th cells from T1D compared to HC (p=0.04 and p=0.005, respectively). In addition, by stratifying subjects into VDR FokI genotypes, significant lower percentage of CD4(+) cells was observed in 25(OH)D3 and 1,25(OH)2D3 stimulated Th cells from T1D patients carrying the "FF" genotype compared to those with the genotypes "Ff/ff" (p=0.02 and p=0.05, respectively). Moreover, looking at vitamin D effects according to VDR FokI genotypes, CD4(+) cells were significantly down-regulated by 25(OH)D3 and 1,25(OH)2D3 only in T1D "FF" carriers (p=0.01 and p=0.02; respectively). According to these results, T1D patients carrying the "FF" genotype with an adequate vitamin D therapy may benefit from a more balanced T cell immunity. However, further research is needed to confirm these premilinary findings and to elucidate functional mechanisms of genetic variation in the vitamin D system. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

Morán-Auth Y ，Penna-Martinez M ，Badenhoop K 《-》

Osteogenic induction and 1,25-dihydroxyvitamin D3 oppositely regulate the proliferation and expression of RANKL and the vitamin D receptor of human periodontal ligament cells.

Tang X ，Meng H 《-》