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

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 [eve[, 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-1 alpha C-889T, IL-1 beta C+3962T, IL-1 beta 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: IFN gamma AUTR5644T,TNF alpha A-308G, and IL-10 A-1082G. The SNPs were inserted in a Cox regression mode( 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 mode[, the relative risk to develop a severe ventilatory restriction was increased by the antitopoisomerase I antibody (p = 0.01; HR = 14.67, Cl-95 = 1.87-114.92), the dcSSc subset (p = 0.007; HR = 3.14, Cl-95 = 1.36-7.21) and the IL-1 beta C + 3962T SNP (p = 0.003 TT vs CC; HR = 6.61, Cl-95 = 2.28-19.15). The IL-1 beta C + 3962T SNP is associated with the presence of severe restrictive lung physiology in Italian SSc patients. (c) 2007 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.