Browse by author
Lookup NU author(s): Professor Jaap Van Laar
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
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 [P-MH = 1.92 x 10(-5) odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (P-MH = 4.84 x 10(-3) OR = 1.12). The second follow-up phase confirmed this finding (P-chi 2 = 2.82 x 10(-4) OR = 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 (P-MH = 2.82 x 10(-9) OR = 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.
Author(s): Bossini-Castillo L, Martin JE, Broen J, Gorlova O, Simeon CP, Beretta L, Vonk MC, Callejas JL, Castellvi I, Carreira P, Garcia-Hernandez FJ, Castro MF, Coenen MJH, Riemekasten G, Witte T, Hunzelmann N, Kreuter A, Distler JHW, Koeleman BP, Voskuyl AE, Schuerwegh AJ, Palm O, Hesselstrand R, Nordin A, Airo P, Lunardi C, Scorza R, Shiels P, van Laar JM, Herrick A, Worthington J, Denton C, Tan FK, Arnett FC, Agarwal SK, Assassi S, Fonseca C, Mayes MD, Radstake TRDJ, Martin J, Spanish Scleroderma Grp
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
Year: 2012
Volume: 21
Issue: 4
Pages: 926-933
Print publication date: 10/11/2011
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/hmg/ddr522
DOI: 10.1093/hmg/ddr522
Altmetrics provided by Altmetric