title: Vitamin D receptor polymorphisms and expression profile in rheumatoid arthritis Brazilian patients.
abstract: 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.
authors.affiliation: Department of Genetics, Federal University of Pernambuco, Recife, Pernambuco, Brazil.|Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco, Av. Moraes Rego, 1235, CEP 50760-901, Recife, Pernambuco, Brazil.
authors.forename: Catarina Addobbati Jordão
authors.initials: CA
authors.lastname: Cavalcanti
authors.affiliation: Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco, Av. Moraes Rego, 1235, CEP 50760-901, Recife, Pernambuco, Brazil. j.azvedo@gmail.com.
authors.forename: Jaqueline de Azevêdo
authors.initials: Jde A
authors.lastname: Silva
authors.affiliation: Department of Antibiotics, Federal University of Pernambuco, Recife, Pernambuco, Brazil.
authors.forename: Will de Barros
authors.initials: Wde B
authors.lastname: Pita
authors.affiliation: Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Tiago Degani
authors.initials: TD
authors.lastname: Veit
authors.affiliation: Division of Rheumatology, Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Odirlei Andre
authors.initials: OA
authors.lastname: Monticielo
authors.affiliation: Division of Rheumatology, Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Ricardo Machado
authors.initials: RM
authors.lastname: Xavier
authors.affiliation: Division of Rheumatology, Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: João Carlos Tavares
authors.initials: JC
authors.lastname: Brenol
authors.affiliation: Division of Rheumatology, Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Cleiton Viegas
authors.initials: CV
authors.lastname: Brenol
authors.affiliation: Rheumatology Service, Clinical Hospital, Federal University of Alagoas, Maceió, Alagoas, Brazil.
authors.forename: Thiago Sotero
authors.initials: TS
authors.lastname: Fragoso
authors.affiliation: Rheumatology Division, Clinical Hospital, Federal University of Pernambuco, Recife, Pernambuco, Brazil.
authors.forename: Alexandre Domingues
authors.initials: AD
authors.lastname: Barbosa
authors.affiliation: Rheumatology Division, Clinical Hospital, Federal University of Pernambuco, Recife, Pernambuco, Brazil.
authors.forename: Ângela Luiza Branco Pinto
authors.initials: ÂL
authors.lastname: Duarte
authors.affiliation: Clinical Immunology Division, Department of Medicine, Medicine Faculty of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Renê Donizeti Ribeiro
authors.initials: RD
authors.lastname: Oliveira
authors.affiliation: Clinical Immunology Division, Department of Medicine, Medicine Faculty of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Paulo
authors.initials: P
authors.lastname: Louzada-Júnior
authors.affiliation: Clinical Immunology Division, Department of Medicine, Medicine Faculty of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Eduardo Antônio
authors.initials: EA
authors.lastname: Donadi
authors.affiliation: Department of Genetics, Federal University of Pernambuco, Recife, Pernambuco, Brazil.|Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco, Av. Moraes Rego, 1235, CEP 50760-901, Recife, Pernambuco, Brazil.
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
authors.affiliation: Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: José Artur Bogo
authors.initials: JA
authors.lastname: Chies
authors.affiliation: Department of Genetics, Federal University of Pernambuco, Recife, Pernambuco, Brazil.|Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco, Av. Moraes Rego, 1235, CEP 50760-901, Recife, Pernambuco, Brazil.
authors.forename: Paula
authors.initials: P
authors.lastname: Sandrin-Garcia
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics*; D001938:Brazil; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000097:blood / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human
keywords: Monocytes; Rheumatoid arthritis; SNPs; VDR; mRNA