The arachidonate 5-lipoxygenase activating protein gene polymorphism is associated with the risk of scleroderma-related interstitial lung disease: A multicentre European Scleroderma Trials and Research group (EUSTAR) study

Otylia Kowal-Bielecka*, Sylwia Chwiesko-Minarowska, Pawel L. Bernatowicz, Yannick Allanore, Timothy Radstake, Marco Matucci-Cerinic, Jasper Broen, Roger Hesselstrand, Dorota Krasowska, Gabriella Riemekasten, Madelon Vonk, Oksana Kowalczuk, Marek Bielecki, Robert Milewski, Lech Chyczewski, Jacek Niklinski, Krzysztof Kowal

*Corresponding author for this work
5 Citations (Scopus)

Abstract

Objectives. The arachidonate 5-lipoxygenase activating protein (ALOX5AP) regulates synthesis of leukotrienes (LTs), which are important mediators of inflammation and connective tissue remodelling. The aim of this study was to evaluate if single nucleotide polymorphisms (SNPs) of ALOX5AP confer risk of SSc and/ or SSc-related organ involvement. Methods. Seven SNPs of ALOX5AP (rs17222814, rs17216473, rs10507391, rs4769874, rs9551963, rs9315050 and rs7222842) were genotyped in a cohort of 977 patients with SSc and 558 healthy controls from centres collaborating within the European Scleroderma Trials and Research group. In 22 SSc patients, concentrations of cysteinyl LTs and LT B4 (LTB4) were measured in the supernatants of ionophorestimulated peripheral blood mononuclear cells (PBMCs) by means of commercially available enzyme immunoassay kits. Results. Significant association was found between rs10507391 polymorphism (T/A) of ALOX5AP and the risk of SSc [odds ratio (OR) 1.27 (95% CI 1.07, 1.50), P < 0.05 vs controls], the presence of SSc-related interstitial lung disease on high-resolution CT of the lungs [OR 1.45 (95% CI 1.17, 1.79), P < 0.05 vs patients without SSc-related interstitial lung disease] as well as with restrictive ventilatory defect [forced vital capacity < 70% of predicted; OR 1.51 (95% CI 1.16, 1.97), P < 0.05 vs SSc patients without pulmonary restriction]. PBMCs from SSc carriers of rs10507391 allele A synthesized greater amounts of cysteinyl LTs as compared with SSc patients with rs10507391 TT genotype (P < 0.05). Synthesis of LTB4 did not differ significantly between the two groups. Conclusion. The results of our study indicate that the genetic variants of ALOX5AP might play a role in the development of SSc-related pulmonary fibrosis.

Original languageEnglish
JournalRheumatology (United Kingdom)
Volume56
Issue number5
Pages (from-to)844-852
Number of pages9
ISSN1462-0324
DOIs
Publication statusPublished - 01.05.2017

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

Fingerprint

Dive into the research topics of 'The arachidonate 5-lipoxygenase activating protein gene polymorphism is associated with the risk of scleroderma-related interstitial lung disease: A multicentre European Scleroderma Trials and Research group (EUSTAR) study'. Together they form a unique fingerprint.

Cite this