RT Journal Article
SR Electronic
T1 An MIF Promoter Polymorphism Is Associated with Susceptibility to Pulmonary Arterial Hypertension in Diffuse Cutaneous Systemic Sclerosis
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.161369
DO 10.3899/jrheum.161369
A1 Lara Bossini-Castillo
A1 Diana Campillo-Davó
A1 Elena López-Isac
A1 Francisco David  Carmona
A1 Carmen P.  Simeon
A1 Patricia Carreira
A1 José Luis  Callejas-Rubio
A1 Iván Castellví
A1 Antonio Fernández-Nebro
A1 Luis Rodríguez-Rodríguez
A1 Manel Rubio-Rivas
A1 Francisco J.  García-Hernández
A1 Ana Belén  Madroñero
A1 Lorenzo Beretta
A1 Alessandro Santaniello
A1 Claudio Lunardi
A1 Paolo Airó
A1 Anna-Maria Hoffmann-Vold
A1 Alexander Kreuter
A1 Gabriela Riemekasten
A1 Torsten Witte
A1 Nicolas Hunzelmann
A1 Madelon C.  Vonk
A1 Alexandre E.  Voskuyl
A1 J.  de Vries-Bouwstra
A1 Paul Shiels
A1 Ariane Herrick
A1 Jane Worthington
A1 Timothy R.D.J.  Radstake
A1 Javier Martin
A1 the Spanish Scleroderma Group
YR 2017
UL http://www.jrheum.org/content/early/2017/06/26/jrheum.161369.abstract
AB Objective Systemic sclerosis (SSc) is a fibrotic immune-mediated disease of unknown etiology. Among its clinical manifestations, pulmonary involvement is the leading cause of mortality in patients with SSc. However, the genetic factors involved in lung complication are not well defined. We aimed to review the association of the MIF gene, which encodes a cytokine implicated in idiopathic pulmonary hypertension among other diseases, with the susceptibility and clinical expression of SSc, in addition to testing the association of this polymorphism with SSc-related pulmonary involvement. Methods A total of 4392 patients with SSc and 16,591 unaffected controls from 6 cohorts of European origin were genotyped for the MIF promoter variant rs755622. An inverse variance method was used to metaanalyze the data. Results A statistically significant increase of the MIF rs755622*C allele frequency compared with controls was observed in the subgroups of patients with diffuse cutaneous SSc (dcSSc) and with pulmonary arterial hypertension (PAH) independently (dcSSc: p = 3.20E–2, OR 1.13; PAH: p = 2.19E– 02, OR 1.32). However, our data revealed a stronger effect size with the subset of patients with SSc showing both clinical manifestations (dcSSc with PAH: p = 6.91E–3, OR 2.05). Conclusion We reviewed the association of the MIF rs755622*C allele with SSc and described a phenotype-specific association of this variant with the susceptibility to develop PAH in patients with dcSSc.