An MIF promoter polymorphism is associated with susceptibility to pulmonary arterial hypertension in diffuse cutaneous systemic sclerosis

Lara Bossini-Castillo, Diana Campillo-Davo, Elena Lopez-Isac*, Francisco David Carmona, Carmen P. Simeon, Patricia Carreira, Jose Luis Callejas-Rubio, Ivan Castellvi, Antonio Fernandez-Nebro, Luis Rodriguez-Rodriguez, Manel Rubio-Rivas, Francisco J. Garcia-Hernandez, Ana Belen Madronero, Lorenzo Beretta, Alessandro Santaniello, Claudio Lunardi, Paolo Airo, Anna Maria Hoffmann-Vold, Alexander Kreuter, Gabriela RiemekastenTorsten Witte, Nicolas Hunzelmann, Madelon C. Vonk, Alexandre E. Voskuyl, J. De Vries-Bouwstra, Paul Shiels, Ariane Herrick, Jane Worthington, Timothy R.D.J. Radstake, Javier Martin, Spanish Scleroderma Group

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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 rs755622C 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.

Original languageEnglish
Pages (from-to)1453-1457
Number of pages5
JournalJournal of Rheumatology
Issue number10
Publication statusPublished - 1 Oct 2017

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