Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/106045
Title: | Influence of TYK2 in systemic sclerosis susceptibility: a new locus in the IL-12 pathway |
Author: | López Isac, Elena Campillo Davo, Diana Bossini Castillo, Lara Guerra, Sandra G. Assassi, Shervin Simeón Aznar, Carmen Pilar Carreira, Patricia Ortego Centeno, Norberto García de la Peña, Paloma Beretta, Lorenzo Santaniello, Alessandro Bellocchi, Chiara Lunardi, Claudio Moroncini, Gianluca Gabrielli, Armando Riemestaken, Gabriela Witte, Torsten Hunzelmann, Nicolas Kreuter, Alexander Distler, Jörg H.V. Voskuyl, Alexandre E. Vries-Bouwstra, Jeska de Herrick, Ariane L. Worthington, Jane Denton, Christopher P. Fonseca, Carmen Radstake, Timothy R.D.J. Mayes, Maureen D. Martín, Javier Spanish Scleroderma Study Group (SSSG) Espinosa Garriga, Gerard |
Keywords: | Citoquines Genètica humana Genètica mèdica Malalties autoimmunitàries Polimorfisme genètic Cytokines Human genetics Medical genetics Autoimmune diseases Genetic polymorphisms |
Issue Date: | 2-Sep-2015 |
Publisher: | BMJ Publishing Group |
Abstract: | OBJECTIVES: TYK2 is a common genetic risk factor for several autoimmune diseases. This gene encodes a protein kinase involved in interleukin 12 (IL-12) pathway, which is a well-known player in the pathogenesis of systemic sclerosis (SSc). Therefore, we aimed to assess the possible role of this locus in SSc. METHODS: This study comprised a total of 7103 patients with SSc and 12 220 healthy controls of European ancestry from Spain, USA, Germany, the Netherlands, Italy and the UK. Four TYK2 single-nucleotide polymorphisms (V362F (rs2304256), P1104A (rs34536443), I684S (rs12720356) and A928V (rs35018800)) were selected for follow-up based on the results of an Immunochip screening phase of the locus. Association and dependence analyses were performed by the means of logistic regression and conditional logistic regression. Meta-analyses were performed using the inverse variance method. RESULTS: Genome-wide significance level was reached for TYK2 V362F common variant in our pooled analysis (p=3.08×10(-13), OR=0.83), while the association of P1104A, A928V and I684S rare and low-frequency missense variants remained significant with nominal signals (p=2.28×10(-3), OR=0.80; p=1.27×10(-3), OR=0.59; p=2.63×10(-5), OR=0.83, respectively). Interestingly, dependence and allelic combination analyses showed that the strong association observed for V362F with SSc, corresponded to a synthetic association dependent on the effect of the three previously mentioned TYK2 missense variants. CONCLUSIONS: We report for the first time the association of TYK2 with SSc and reinforce the relevance of the IL-12 pathway in SSc pathophysiology. |
Note: | Reproducció del document publicat a: https://doi.org/10.1136/annrheumdis-2015-208154 |
It is part of: | Annals of the Rheumatic Diseases, 2015, vol. 75, num. 8, p. 1521-1526 |
URI: | http://hdl.handle.net/2445/106045 |
Related resource: | https://doi.org/10.1136/annrheumdis-2015-208154 |
ISSN: | 0003-4967 |
Appears in Collections: | Articles publicats en revistes (Medicina) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
663906.pdf | 919.67 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.