title: Interleukin-1 gene complex polymorphisms in systemic sclerosis patients with severe restrictive lung physiology.
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-1alpha C-889T, IL-1beta C+3962T, IL-1beta 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: IFNgamma AUTR5644T, TNFalpha 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, CI95=1.87-114.92), the dcSSc subset (p=0.007; HR=3.14, CI95=1.36-7.21) and the IL-1beta C+3962T SNP (p=0.003 TT vs CC; HR=6.61, CI95=2.28-19.15). The IL-1beta C+3962T SNP is associated with the presence of severe restrictive lung physiology in Italian SSc patients.
authors.affiliation: Unit of Clinical Immunology and Allergology, IRCCS Fondazione Policlinico-Mangiagalli-Regina Elena and University of Milan, Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Beretta
authors.forename: Francesca
authors.initials: F
authors.lastname: Bertolotti
authors.forename: Francesca
authors.initials: F
authors.lastname: Cappiello
authors.forename: Morena
authors.initials: M
authors.lastname: Barili
authors.forename: Michela
authors.initials: M
authors.lastname: Masciocchi
authors.forename: Karen
authors.initials: K
authors.lastname: Toussoun
authors.forename: Monica
authors.initials: M
authors.lastname: Caronni
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scorza
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics* / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics* / Q000276:immunology; D007558:Italy; D008173:Lung Diseases, Obstructive / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology
chemical_list: D016207:Cytokines; D053582:Interleukin-1alpha; D053583:Interleukin-1beta