2024-03-29T02:27:57Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/664242021-12-28T15:58:25Zcom_10261_64com_10261_1col_10261_317
2013-02-08T12:12:24Z
urn:hdl:10261/66424
A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations
Bossini-Castillo, L.
Martín, J. E.
Broen, Jasper C.
Gorlova, Olga
Simeón, Carmen P.
Beretta, L.
Vonk, Madelon C.
Callejas-Rubio, J. L.
Castellví, I.
Carreira, P.
García-Hernández, Francisco José
Castro, M. F.
Coenen, M. J.
Riemekasten, G.
Witte, Torsten
Hunzelmann, Nicolas
Kreuter, A.
Distler, J. H.
Koeleman, B. P.
Voskuyl, Alexandre E.
Schuerwegh, A. J.
Palm, Øyvind
Hesselstrand, R.
Nordin, A.
Airó, Paolo
Lunardi, C.
Scorza, R.
Shiels, Paul G.
Laar, Jacob M. van
Herrick, A.
Worthington, J.
Denton, C.
Tan, F. K.
Arnett, F. C.
Agarwal, S. K.
Assassi, S.
Fonseca, C.
Mayes, Maureen D.
Radstake, T. R.
Martín, J.
A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow-up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [PMH5 1.92 3 10 -5 odds ratio (OR) 5 1.19] as the genetic variant with the firmest independent association observed in the analyzedGWASpeak of association. After the first follow-up phase, only the association of rs3790567 was consistent (PMH5 4.84 3 10 -3OR 5 1.12). The second follow-up phase confirmed this finding (Px2 5 2.82 3 10 -4 OR 5 1.34). After performing overall pooled-analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (PMH5 2.82 3 10 -9 OR 5 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis. © The Author 2011. Published by Oxford University Press. All rights reserved.
2013-02-08T12:12:24Z
2013-02-08T12:12:24Z
2012
2013-02-08T12:12:24Z
artículo
Human Molecular Genetics 21: 926- 933 (2012)
http://hdl.handle.net/10261/66424
10.1093/hmg/ddr522
22076442
eng
closedAccess
Oxford University Press