Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/113070
Title: A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides
Author: Bossini Castillo, Lara
Kovel, C. de
Kallberg, H.
Slot, R. van 't
Italiaander, A.
Coenen, M.
Tak, P. P.
Posthumus, M. D.
Wijmenga, Cisca
Huizinga, Tom
Helm-van Mil, A. H. M. van der
Stoeken-Rijsbergen, G.
Rodríguez Rodríguez, Luis
Balsa, Alejandro
González Álvaro, Isidoro
González Gay, Miguel A.
Gómez Vaquero, Carmen
Franke, B.
LifeLines Cohort Study
Vermeulen, S.
Horst-Bruinsma, I. E. van der
Dijkmans, B. A. C.
Wolbink, G. J.
Ophoff, R. A.
Maehlen, M. T.
Riel, P. van
Merriman, M.
Klareskog, L.
Lie, Benedicte A.
Merriman, Tony
Crusius, J. B. A.
Brouwer, E.
Martin, Javier
Vries, N. de
Toes, R.
Padyukov, L.
Koeleman, Bobby P. C.
Keywords: Artritis reumatoide
Genomes
Genòmica
Anticossos monoclonals
Pèptids
Rheumatoid arthritis
Genomes
Genomics
Monoclonal antibodies
Peptides
Issue Date: Mar-2015
Publisher: BMJ Publishing Group
Abstract: Introduction. Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA. Methods. We performed a large-scale genome-wide association study (GWAS) in three Caucasian European cohorts comprising 1148 ACPA-negative RA patients and 6008 controls. All patients were screened using the Illumina Human Cyto-12 chip, and controls were genotyped using different genome-wide platforms. Population-independent analyses were carried out by means of logistic regression. Meta-analysis with previously published data was performed as follow-up for selected signals (reaching a total of 1922 ACPA-negative RA patients and 7087 controls). Imputation of classical HLA alleles, aminoacid residues and single nucleotide polymorphisms was undertaken. Results. The combined analysis of the studied cohorts resulted in identification of a peak of association in the HLA-region and several suggestive non-HLA associations. Meta-analysis with previous reports confirmed the association of the HLA region with this subset and an observed association in the CLYBL locus remained suggestive. The imputation and deep interrogation of the HLA region led to identification of a two aminoacid model (HLA-B at position 9 and HLA-DRB1 at position 11) that accounted for the observed genome-wide associations in this region. Conclusions. Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition.
Note: Reproducció del document publicat a: https://doi.org/10.1136/annrheumdis-2013-204591
It is part of: Annals of the Rheumatic Diseases, 2015, vol. 74, num. 3, p. e15
Related resource: https://doi.org/10.1136/annrheumdis-2013-204591
URI: http://hdl.handle.net/2445/113070
ISSN: 0003-4967
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)

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