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 Riemekasten & 11 others Torsten 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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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
Volume44
Issue number10
DOIs
Publication statusPublished - 1 Oct 2017

Cite this

Bossini-Castillo, L., Campillo-Davo, D., Lopez-Isac, E., Carmona, F. D., Simeon, C. P., Carreira, P., ... Spanish Scleroderma Group (2017). An MIF promoter polymorphism is associated with susceptibility to pulmonary arterial hypertension in diffuse cutaneous systemic sclerosis. Journal of Rheumatology, 44(10), 1453-1457. https://doi.org/10.3899/jrheum.161369
Bossini-Castillo, Lara ; Campillo-Davo, Diana ; Lopez-Isac, Elena ; Carmona, Francisco David ; Simeon, Carmen P. ; Carreira, Patricia ; Callejas-Rubio, Jose Luis ; Castellvi, Ivan ; Fernandez-Nebro, Antonio ; Rodriguez-Rodriguez, Luis ; Rubio-Rivas, Manel ; Garcia-Hernandez, Francisco J. ; Madronero, Ana Belen ; Beretta, Lorenzo ; Santaniello, Alessandro ; Lunardi, Claudio ; Airo, Paolo ; Hoffmann-Vold, Anna Maria ; Kreuter, Alexander ; Riemekasten, Gabriela ; Witte, Torsten ; Hunzelmann, Nicolas ; Vonk, Madelon C. ; Voskuyl, Alexandre E. ; De Vries-Bouwstra, J. ; Shiels, Paul ; Herrick, Ariane ; Worthington, Jane ; Radstake, Timothy R.D.J. ; Martin, Javier ; Spanish Scleroderma Group. / An MIF promoter polymorphism is associated with susceptibility to pulmonary arterial hypertension in diffuse cutaneous systemic sclerosis. In: Journal of Rheumatology. 2017 ; Vol. 44, No. 10. pp. 1453-1457.
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title = "An MIF promoter polymorphism is associated with susceptibility to pulmonary arterial hypertension in diffuse cutaneous systemic sclerosis",
abstract = "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.",
keywords = "Mif rs755622, Pulmonary arterial hypertension, Systemic sclerosis",
author = "Lara Bossini-Castillo and Diana Campillo-Davo and Elena Lopez-Isac and Carmona, {Francisco David} and Simeon, {Carmen P.} and Patricia Carreira and Callejas-Rubio, {Jose Luis} and Ivan Castellvi and Antonio Fernandez-Nebro and Luis Rodriguez-Rodriguez and Manel Rubio-Rivas and Garcia-Hernandez, {Francisco J.} and Madronero, {Ana Belen} and Lorenzo Beretta and Alessandro Santaniello and Claudio Lunardi and Paolo Airo and Hoffmann-Vold, {Anna Maria} and Alexander Kreuter and Gabriela Riemekasten and Torsten Witte and Nicolas Hunzelmann and Vonk, {Madelon C.} and Voskuyl, {Alexandre E.} and {De Vries-Bouwstra}, J. and Paul Shiels and Ariane Herrick and Jane Worthington and Radstake, {Timothy R.D.J.} and Javier Martin and {Spanish Scleroderma Group}",
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pages = "1453--1457",
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Bossini-Castillo, L, Campillo-Davo, D, Lopez-Isac, E, Carmona, FD, Simeon, CP, Carreira, P, Callejas-Rubio, JL, Castellvi, I, Fernandez-Nebro, A, Rodriguez-Rodriguez, L, Rubio-Rivas, M, Garcia-Hernandez, FJ, Madronero, AB, Beretta, L, Santaniello, A, Lunardi, C, Airo, P, Hoffmann-Vold, AM, Kreuter, A, Riemekasten, G, Witte, T, Hunzelmann, N, Vonk, MC, Voskuyl, AE, De Vries-Bouwstra, J, Shiels, P, Herrick, A, Worthington, J, Radstake, TRDJ, Martin, J & Spanish Scleroderma Group 2017, 'An MIF promoter polymorphism is associated with susceptibility to pulmonary arterial hypertension in diffuse cutaneous systemic sclerosis' Journal of Rheumatology, vol. 44, no. 10, pp. 1453-1457. https://doi.org/10.3899/jrheum.161369

An MIF promoter polymorphism is associated with susceptibility to pulmonary arterial hypertension in diffuse cutaneous systemic sclerosis. / Bossini-Castillo, Lara; Campillo-Davo, Diana; Lopez-Isac, Elena; Carmona, Francisco David; Simeon, Carmen P.; Carreira, Patricia; Callejas-Rubio, Jose Luis; Castellvi, Ivan; Fernandez-Nebro, Antonio; Rodriguez-Rodriguez, Luis; Rubio-Rivas, Manel; Garcia-Hernandez, Francisco J.; Madronero, Ana Belen; Beretta, Lorenzo; Santaniello, Alessandro; Lunardi, Claudio; Airo, Paolo; Hoffmann-Vold, Anna Maria; Kreuter, Alexander; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Vonk, Madelon C.; Voskuyl, Alexandre E.; De Vries-Bouwstra, J.; Shiels, Paul; Herrick, Ariane; Worthington, Jane; Radstake, Timothy R.D.J.; Martin, Javier; Spanish Scleroderma Group.

In: Journal of Rheumatology, Vol. 44, No. 10, 01.10.2017, p. 1453-1457.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - An MIF promoter polymorphism is associated with susceptibility to pulmonary arterial hypertension in diffuse cutaneous systemic sclerosis

AU - Bossini-Castillo, Lara

AU - Campillo-Davo, Diana

AU - Lopez-Isac, Elena

AU - Carmona, Francisco David

AU - Simeon, Carmen P.

AU - Carreira, Patricia

AU - Callejas-Rubio, Jose Luis

AU - Castellvi, Ivan

AU - Fernandez-Nebro, Antonio

AU - Rodriguez-Rodriguez, Luis

AU - Rubio-Rivas, Manel

AU - Garcia-Hernandez, Francisco J.

AU - Madronero, Ana Belen

AU - Beretta, Lorenzo

AU - Santaniello, Alessandro

AU - Lunardi, Claudio

AU - Airo, Paolo

AU - Hoffmann-Vold, Anna Maria

AU - Kreuter, Alexander

AU - Riemekasten, Gabriela

AU - Witte, Torsten

AU - Hunzelmann, Nicolas

AU - Vonk, Madelon C.

AU - Voskuyl, Alexandre E.

AU - De Vries-Bouwstra, J.

AU - Shiels, Paul

AU - Herrick, Ariane

AU - Worthington, Jane

AU - Radstake, Timothy R.D.J.

AU - Martin, Javier

AU - Spanish Scleroderma Group

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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.

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 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.

KW - Mif rs755622

KW - Pulmonary arterial hypertension

KW - Systemic sclerosis

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U2 - 10.3899/jrheum.161369

DO - 10.3899/jrheum.161369

M3 - Article

VL - 44

SP - 1453

EP - 1457

JO - Journal of Rheumatology

JF - Journal of Rheumatology

SN - 0315-162X

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