Interleukin-1 gene complex polymorphisms in systemic sclerosis patients with severe restrictive lung physiology

Lorenzo Beretta, Francesca Bertolotti, Francesca Cappiello, Morena Barili, Michela Masciocchi, Karen Toussoun, Monica Caronni, Raffaella Scorza

Research output: Contribution to journalArticle

Abstract

Increased concentrations of interleukin-1 (IL-1) were observed in bronchoalveolar lavage fluids from patients with systemic sclerosis (SSc), and their levels were correlated with the patients' forced vital capacity (FVC). Because IL-1 production is regulated at the genetic level, we hypothesized that IL-1 gene complex single nucleotide polymorphisms (SNPs) might be relevant to the progression of ventilatory restriction in SSc. Two-hundred four Italian SSc patients were genotyped for the following IL-1 gene complex SNPs: IL-1α C-889T, IL-1β C+3962T, IL-1β C-511T, IL-1R Cpst1970T, and IL-1Ra Cmspal11100T, as well as for the following SNPs of cytokines with regulatory functions on IL-1 production: IFNγ AUTR5644T, TNFα A-308G, and IL-10 A-1082G. The SNPs were inserted in a Cox regression model with disease subset, gender, autoantibodies, age at onset of disease, and prior use of immunosoppresants as covariates and the presence of FVC <55% of predicted values as outcome measure; p values were corrected for the number of pairwise comparisons. Twenty-five patients (12.3%) developed a severe ventilatory restriction after 6.8 ± 6.6 years (mean ± standard deviation) from diagnosis. In our model, the relative risk to develop a severe ventilatory restriction was increased by the antitopoisomerase I antibody (p = 0.01; HR = 14.67, CI 95 = 1.87-114.92), the dcSSc subset (p = 0.007; HR = 3.14, CI 95 = 1.36-7.21) and the IL-1β C+3962T SNP (p = 0.003 TT vs CC; HR = 6.61, CI 95 = 2.28-19.15). The IL-1β C+3962T SNP is associated with the presence of severe restrictive lung physiology in Italian SSc patients.

Original languageEnglish
Pages (from-to)603-609
Number of pages7
JournalHuman Immunology
Volume68
Issue number7
DOIs
Publication statusPublished - Jul 2007

Keywords

  • Interleukin-1
  • Interstitial lung disease
  • Single nucleotide polymorphism
  • Systemic sclerosis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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