Genetic Susceptibility Loci in Rheumatoid Arthritis Establish Transcriptional Regulatory Networks with Other Genes


Autoria(s): SILVA, Guilherme Liberato; JUNTA, Cristina Moraes; SAKAMOTO-HOJO, Elza Tiemi; DONADI, Eduardo Antonio; LOUZADA-JUNIOR, Paulo; PASSOS, Geraldo A. S.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2009

Resumo

Linkage studies have identified the human leukocyte antigen (HLA)-DRB1 as a putative rheumatoid arthritis (RA) susceptibility locus (SL). Nevertheless, it was estimated that its contribution was partial, suggesting that other non-HLA genes may play a role in RA susceptibility. To test this hypothesis, we conducted microarray transcription profiling of peripheral blood mononuclear cells in 15 RA patients and analyzed the data, using bioinformatics programs (significance analysis of microarrays method and GeneNetwork), which allowed us to determine the differentially expressed genes and to reconstruct transcriptional networks. The patients were grouped according to disease features or treatment with tumor necrosis factor blocker. Transcriptional networks that were reconstructed allowed us to identify the interactions occurring between RA SL and other genes, for example, HLA-DRB1 interacting with FNDC3A (fibronectin type III domain containing 3A). Given that fibronectin fragments can stimulate mediators of matrix and cartilage destruction in RA, this interaction is of special interest and may contribute to a clearer understanding of the functional role of HLA-DRB1 in RA pathogenesis.

Identificador

Annals of the New York Academy of Sciences, v.1173, p.521-537, 2009

978-1-57331-762-7

0077-8923

http://producao.usp.br/handle/BDPI/24010

10.1111/j.1749-6632.2009.04629.x

http://dx.doi.org/10.1111/j.1749-6632.2009.04629.x

Idioma(s)

eng

Publicador

BLACKWELL PUBLISHING

Relação

Annals of the New York Academy of Sciences

Direitos

restrictedAccess

Copyright BLACKWELL PUBLISHING

Palavras-Chave #rheumatoid arthritis #susceptibility loci #gene expression #gene networks #SYSTEMIC-LUPUS-ERYTHEMATOSUS #GENOME-WIDE ASSOCIATION #HLA-DRB1 SHARED EPITOPE #MICROARRAY ANALYSIS #DISEASE #EXPRESSION #SCAN #ANTIBODIES #THERAPY #THYMUS #Multidisciplinary Sciences
Tipo

article

proceedings paper

publishedVersion