The Influence of Vitamin D Receptor Gene Polymorphisms in Spondyloarthritis

Abstract

Spondyloarthritis (SpA) is an inflammatory rheumatic disease related to low bone mineral density. Because vitamin D plays an important role in bone metabolism and immune system modulation, the aim of this study was to evaluate the influence of polymorphisms in vitamin D receptor genes (VDR) in the development of SpA. In this case–control study, a total of 244 patients with SpA and 197 individuals with no SpA were included. Among the patients, 174 had ankylosing spondylitis (AS) and 66 had psoriatic arthritis (PsA). Genotyping of FokI (rs2228570 C > T), BsmI (rs1544410 C > T), ApaI (rs7975232 A > C), and TaqI (rs731236 T > C) was performed using PCR-RFLP, while genotyping of HLA-B ∗ 27 was performed using PCR-SSP. Serum levels for hydroxy (OH) vitamin D and the clinical activity index of the disease (BASDAI) were also evaluated. SNPStats and OpenEpi software were used for statistical analysis. The ApaI a allele and ApaI a/a genotype were less frequent in PsA compared with controls. The ApaI a/a genotype was associated with a protecting factor for PsA in females, and ApaI A/a was associated with a protecting factor for the disease in HLA-B ∗ 27 positive patients. Notwithstanding, the ApaI a/a genotype was a risk factor for SpA and AS in males. The FokI f/f genotype was associated with a better clinical activity in PsA. When considering the covariates, vitamin D sufficiency, and gender, the FokI F/F genotype was associated with a risk factor in males with SpA and AS compared with females with this same genotype. In conclusion, the ApaI rs7975232 polymorphism was associated with PsA, and the FokI rs2228570 polymorphism was associated with better clinical PsA activity. ApaI and FokI were associated with SpA and AS when considering gender and vitamin D sufficiency.

IL17F: A Possible Risk Marker for Spondyloarthritis in HLA-B*27 Negative Brazilian Patients

“…Research conducted by our group showed that VDR, TNF and IL17 polymorphisms were associated to the SpA [12,13]. The association of these polymorphisms in patients with absence of HLA-B*27 was not performed and, in this study, we assessed whether the polymorphisms in IL17, TNF and VDR genes influence the development of SpA in patients who were HLA-B*27 negative.…”

“…Previous studies carried out in our laboratory have shown the association of VDR ApaI and FokI polymorphisms with PsA [12], and TNF and IL17 variants, which influence the good production of the respective cytokines, were associated with SpA, AS and PsA regardless of gender and HLA-B*27 [13]. In both, the HLA-B*27 was considered a covariate in multivariate analysis, but patients who were negative for HLA-B*27 were not investigated.…”

Vitamin D Signaling in Gastro-Rheumatology: From Immuno-Modulation to Potential Clinical Applications

“…ApaI a/a was demonstrated to be a protective factor for PsA and for women with PsA, and ApaI A/a was a protective factor for PsA patients who were HLA-B27 positive. In this context, the ApaI a allele correlated with higher levels of vitamin D in the serum, and FokI polymorphism was associated with lower bone mineral density [106][107][108]. In a recent meta-analysis pooling data from nine studies, Xue et al found a significant increase in CD risk for TaqI polymorphism in Europeans and in UC risk for FokI polymorphism in Asians [109].…”

“…In fact, some of the most common VDR polymorphisms, such as TaqI and FokI, are likely to affect VDR expression and functionality. Since omozygotic altered genotypes could be present in almost 15-20% of IBD and SpA patients [106,109], possible altered response to vitamin D supplements in this subset of patients needs to be considered. In addition, VDR expression can be induced or inhibited by numerous endogen and exogen stimuli, and in particular inflammatory mediators may downregulate expression of the receptor and therefore prevent vitamin D local effects, even in the presence of an adequate serum amount of the vitamin.…”

Vitamin D receptor gene polymorphisms and the effectiveness of assisted reproductive technology

“…Важно отметить, что для правильного функционирования биологических систем организма человека в равной степени важным является как присутствие в достаточной концентрации биологически активной молекулы (кальцитриол), так и должное функционирование рецептора (VDR). В литературе присутствуют сведения о роли полиморфизмов VDR в развитии сердечно-сосудистых [7], онкологических [8,9], ревматологических и аутоиммунных заболеваний [10,11] и других патологических состояний. Тем не менее роль полиморфизмов гена VDR в репродукции человека изучена недостаточно.…”