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Increased Risk of Fibrosing Alveolitis Associated with Interleukin-1 Receptor Antagonist and Tumor Necrosis Factor- α Gene Polymorphisms
- Source :
- American Journal of Respiratory and Critical Care Medicine. 162:755-758
- Publication Year :
- 2000
- Publisher :
- American Thoracic Society, 2000.
-
Abstract
- Fibrosing alveolitis (FA) is characterized by persistent inflammation and elevated production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and interleukin-1 receptor antagonist (IL-1ra) in the lung. Single base variations at position +2018 in the IL-1ra gene (IL-1RN) and position -308 in the TNF-alpha gene (TNF-A) are overrepresented in other chronic inflammatory disease populations. We have tested the hypothesis that predisposition to FA may also be influenced by these polymorphisms by genotyping 88 cases and matched controls from England and 61 cases and 103 unmatched controls from Italy. The rarer allele for IL-1RN and TNF-A was designated allele 2 in each case. For IL-1RN allele 2, in the English group, the relative odds of FA were increased in homozygous subjects by an odds ratio (OR) of 10.2 (95% confidence intervals [CI], 1.26 to 81.4; p = 0.03) and for carriers by an OR of 1.85 (95% CI, 0.94 to 3.63; p = 0.075). In the Italian population, the risk of FA was increased, in IL-1RN allele 2 homozygotes (OR, 2.54; 95% CI, 0.68 to 9.50; p = 0.2) and in carriers (OR 2.40; 95% CI, 1.26 to 4.60; p = 0.008). Carriage of TNF-A allele 2 was also associated with increased risk of FA in the English (OR, 1.85; 95% CI, 0.94 to 3.63; p = 0.075) and Italian (OR, 2.50; 95% CI, 1.14 to 5.47; p = 0.022) populations. These data suggest IL-1RN (+2018) allele 2 and TNF-A (-308) allele 2 confer increased risk of developing FA and, therefore, that unopposed IL-1beta and/or excessive TNF-alpha may play a pathophysiologic role in this condition.
- Subjects :
- Male
Pulmonary and Respiratory Medicine
Heterozygote
Genotype
medicine.drug_class
Pulmonary Fibrosis
Sialoglycoproteins
medicine.medical_treatment
Critical Care and Intensive Care Medicine
Odds Ratio
Humans
Medicine
Allele
Alleles
Aged
Polymorphism, Genetic
Tumor Necrosis Factor-alpha
business.industry
Homozygote
Antagonist
Receptors, Interleukin-1
Interleukin
Odds ratio
Middle Aged
Receptor antagonist
Interleukin 1 Receptor Antagonist Protein
Cytokine
Interleukin 1 receptor antagonist
Immunology
Female
Tumor necrosis factor alpha
Disease Susceptibility
business
Subjects
Details
- ISSN :
- 15354970 and 1073449X
- Volume :
- 162
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory and Critical Care Medicine
- Accession number :
- edsair.doi.dedup.....14fa120f2b1e0c9ed614bb619af1d73c