Vitamin D Receptor Gene Polymorphism: An Important Predictor of Arthritis Development

Abstract

Vitamin D is an anti-inflammatory molecule and has a role in prevention of arthritis development. Biologically active form 1, 25(OH)2D3 of vitamin D can only exert its action after binding its definite vitamin D receptor encoded by VDR gene. VDR gene polymorphism leads to dysfunctioning of 1, 25(OH)2D3 ultimately disease onset. The purpose of current study was to evaluate the effect of vitamin D level and VDR gene polymorphism on rheumatoid arthritis and osteoarthritis. Blood samples were collected from case and control after taking written consent. Serum was separated and vitamin D level as determined from each sample by ELISA. DNA was extracted from each blood sample and amplified by using gene specific primers. Genotyping was performed by Sangers sequencing and PCR-RFLP technique. It was found that vitamin D level was not significantly different among patients and controls. The rs10735810, rs1544410, rs7975232, and rs731236 were associated with the onset of arthritis at both allelic and genotypic level (p < 0.01). Nucleotide change on rs10735810 site leads to change of tryptophan with arginine. The frequencies of haplotype CGAT, CGGA, CGGT, CTAA, CTAT, TGAA, TGAT, TGGA, and TTGA were higher in patients and act as risk factors of RA onset, whereas haplotypes CGAT, CGAT, CGGT, CTGA, TGAT, TGGA, TTAA, and TTGA were associated with OA onset. In conclusion, serum vitamin D level may be normal among arthritis patients but polymorphism on VDR gene restricts vitamin D to perform its anti-inflammatory function by altering the 1, 25(OH)2 D3 binding sites.

The Association of Vitamin D Receptor Polymorphisms of FokI and TaqI with Rheumatoid Arthritis in North-East of Iran

“…Our data are consistent with the meta-analysis results by Tizaoui et al who demonstrated the association for both FokI and TaqI polymorphisms with RA (1). A recent study demonstrated the strong association of rs10735810 and rs731236 polymorphisms with the onset of RA in the Pakistani population (22). Within two separate meta-analysis studies by Lee et al and Song et al, results from their analysis showed that there is a significant association between VDR FokI polymorphism and RA, but they reported no evidence linking the TaqI polymorphism to disease (23,24).…”

Vitamin D Receptor Polymorphisms in Sex-Frailty Paradox

“…Since ApaI minor allele per se or in linkage with BsmI is associated with different diseases such as Alzheimer's disease [38], osteoarthritis, rheumatoid arthritis [39], and osteopenia [40], we could speculate that ApaI minor allele is related to the "fragilization" of old women, playing a role in the low 25(OH)D levels in the sex-frailty paradox. The exact mechanism involved and whether there is a causal role is still unclear.…”

Vitamin D and early rheumatoid arthritis

“…Studies have shown the active form of vitamin D, 1,25(OH) 2 D, promotes tolerogenic DC cell function [ 20 , 21 ], maintains the balance of Th1/Th2 cells [ 22 ], suppresses the proinflammatory TH17 phenotype [ 23 – 25 ], and promotes T-regulatory (Treg) cell function [ 26 , 27 ], whilst facilitating migration of T cells to the site of inflammation and phenotype stabilisation [ 28 – 30 ]. Similarly, the vitamin D receptor (VDR), which plays an important role in facilitating PBMC responses to 1,25(OH) 2 D in immune homeostasis [ 31 ], is altered in RA [ 32 ] and VDR polymorphisms are linked to the development of arthritis [ 33 ]. Thus, it is likely that simple measurement of serum 25OHD provides only a limited perspective on the potential impact of vitamin D on diseases such as RA.…”