Polymorphisms of TNFalpha, IL1beta, and IL1RN genes in chronic obstructive pulmonary disease

Biochem Biophys Res Commun. 2005 Apr 22;329(4):1246-52. doi: 10.1016/j.bbrc.2005.02.099.


It is recognized that genetic factors play a role in the susceptibility to COPD. COPD is characterized by airflow limitation. Chronic inflammation causes small airway disease and parenchymal destruction, leading to the airflow limitation. Polymorphisms in pro-inflammatory cytokine genes may confer a risk for the development of COPD. A case-control association study was performed in Japanese population (88 COPD patients and 61 controls) and Egyptian population (106 patients and 72 controls). Genotype and allele frequencies of the TNFalpha -308 G/A and +489 G/A polymorphisms, the IL1beta -511 C/T, -31 T/C, and +3954 C/T polymorphisms, and a VNTR polymorphism in intron 2 of the IL1RN gene were investigated. In addition, pairwise haplotype frequencies were analyzed. When studied independently, none of the polymorphisms were associated with the development of COPD in both populations. However, in the Egyptian population, the distributions of the haplotype (IL1beta -31 T/C : IL1beta +3954 C/T) were significantly different between the COPD patients and the controls (p(corr)=0.0037). Our findings suggest that this haplotype within the IL1beta gene may be involved in the pathogenesis of COPD and that the genetic factors of COPD susceptibility might be different between different populations.

MeSH terms

  • Aged
  • Egypt
  • Female
  • Haplotypes / genetics
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / genetics*
  • Japan
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Restriction Fragment Length
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Sialoglycoproteins / genetics*
  • Tumor Necrosis Factor-alpha / genetics*


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha