TY - JOUR
T1 - Vitamin D receptor polymorphisms and expression profile in rheumatoid arthritis brazilian patients
AU - Cavalcanti, Catarina Addobbati Jordão
AU - de Azevêdo Silva, Jaqueline
AU - de Barros Pita, Will
AU - Veit, Tiago Degani
AU - Monticielo, Odirlei Andre
AU - Xavier, Ricardo Machado
AU - Brenol, João Carlos Tavares
AU - Brenol, Cleiton Viegas
AU - Fragoso, Thiago Sotero
AU - Barbosa, Alexandre Domingues
AU - Duarte, Ângela Luiza Branco Pinto
AU - Oliveira, Renê Donizeti Ribeiro
AU - Louzada-Júnior, Paulo
AU - Donadi, Eduardo Antônio
AU - Crovella, Sergio
AU - Chies, José Artur Bogo
AU - Sandrin-Garcia, Paula
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
KW - Monocytes
KW - mRNA
KW - Rheumatoid arthritis
KW - SNPs
KW - VDR
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U2 - 10.1007/s11033-015-3937-z
DO - 10.1007/s11033-015-3937-z
M3 - Article
C2 - 26686848
AN - SCOPUS:84954362327
VL - 43
SP - 41
EP - 51
JO - Molecular Biology Reports
JF - Molecular Biology Reports
SN - 0301-4851
IS - 1
ER -