Vitamin D receptor polymorphisms and expression profile in rheumatoid arthritis brazilian patients


Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and important joint commitment, being the most common systemic autoimmune disease worldwide. RA displays important genetic background with a variety of genes contributing to the immune balance breakdown. Recent studies have demonstrated that vitamin D, through its receptor (VDR), is able to regulate the immune balance and suppress the autoimmunity process, being a potential target in autoimmune diseases. In the present genetic association study, we assessed 5 Tag single nucleotide polymorphisms (SNPs) (rs11168268, rs2248098, rs1540339, rs4760648 and rs3890733), which cover most of the VDR gene, in three different Brazilian populations (from Northeast, Southeast and South Brazil). We also evaluated the VDR expression profile in whole blood and monocytes from RA patients. For genotyping study, 428 RA patients and 616 healthy controls were genotyped with fluorogenic allele specific probes on an ABI7500 platform. For gene expression study, VDR mRNA levels of 15 RA patients and 26 healthy individuals were assessed by RT-PCR. Our results showed that SNPs rs4760648 and rs3890733 are associated to RA susceptibility (p value = 0.0026, OR 1.31 and p value = 0.0091, OR 1.28 with statistical power = 0.999 and 0.993, respectively). Regarding RA clinical features, the studied SNPs did not show significant associations. The gene expression assays showed that VDR mRNA levels were down regulated in both whole blood (−3.3 fold) and monocytes (−3.2 fold) of RA patients when compared to healthy controls. Our results, the first reported for distinct Brazilian populations, support a role of the VDR gene in the susceptibility to RA.

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Fig. 1
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Fig. 4



American College of Rheumatology

B-actin :

Beta actin


Confidence interval


Disease activity score in 28 joints


Glyceraldehyde-3-phosphate dehydrogenase


Health assessment questionnaire


Human leukocyte antigen




Minimum allele frequency


Odds ratio


Peripheral blood mononuclear cells


Bonferroni’s correction


Phosphate buffered saline


Rheumatoid arthritis


Rheumatoid factor


Roswell Park Memorial Institute 1640 media


Relative quantity


Retinoid X receptor


Standard deviation


Shared epitope


Systemic lupus erythematosus


Single nucleotide polymorphism


T helper 1


T helper 17


T helper 2


Tumor necrosis factor


T regulators


Vitamin D binding protein


Vitamin D receptor gene


Vitamin D response elements


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This work was supported by the following Brazilian funding agencies: CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), FAPESP (Fundação Amparo à Pesquisa do Estado de São Paulo), FAPERGS (Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul), FACEPE (Fundação de Amparo à Ciência e Tecnologia de Pernambuco) and FIPE/HCPA (Fundo de Incentivo à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre).

Authors contribution

C.A.J. Cavalcanti and J. De Azevêdo Silva—conception and design from all experiments, acquisition of data, analysis and interpretation, as well as writing the manuscript. W. De Barros Pita conceived and analyzed the gene expression assays. T.D. Veit, O.A. Monticielo, R.M. Xavier, J.C.T. Brenol and C.V. Brenol were responsible for patient data and biological sample acquisition from all South Brazilian population. T.S. Fragoso, A.D. Barbosa and A.L.B.P. Duarte were responsible for patient data and biological sample acquisition from all Northeast Brazilian population. R. D. R. Oliveira, P. Louzada-Júnior and E. A. Donadi were responsible for patient data and biological sample acquisition from all Southeast Brazilian population. S. Crovella, J. A. B. Chies and P. Sandrin-Garcia participated in drafting the manuscript and revising it critically with insightful contributions. All authors approved the submitted manuscript version.

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Correspondence to Jaqueline de Azevêdo Silva.

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The authors have declared no conflicts of interest.

Additional information

Catarina Addobbati Jordão Cavalcanti and Jaqueline de Azevêdo Silva equally contributed to this work.

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Cavalcanti, C.A.J., de Azevêdo Silva, J., de Barros Pita, W. et al. Vitamin D receptor polymorphisms and expression profile in rheumatoid arthritis brazilian patients. Mol Biol Rep 43, 41–51 (2016).

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  • VDR
  • Rheumatoid arthritis
  • SNPs
  • mRNA
  • Monocytes