Contribution of alpha- and beta-defensins to lung function decline and infection in smokers: an association study

Respir Res. 2006 May 15;7(1):76. doi: 10.1186/1465-9921-7-76.

Abstract

Background: Alpha-defensins, which are major constituents of neutrophil azurophilic granules, and beta-defensins, which are expressed in airway epithelial cells, could contribute to the pathogenesis of chronic obstructive pulmonary disease by amplifying cigarette smoke-induced and infection-induced inflammatory reactions leading to lung injury. In Japanese and Chinese populations, two different beta-defensin-1 polymorphisms have been associated with chronic obstructive pulmonary disease phenotypes. We conducted population-based association studies to test whether alpha-defensin and beta-defensin polymorphisms influenced smokers' susceptibility to lung function decline and susceptibility to lower respiratory infection in two groups of white participants in the Lung Health Study (275 = fast decline in lung function and 304 = no decline in lung function).

Methods: Subjects were genotyped for the alpha-defensin-1/alpha-defensin-3 copy number polymorphism and four beta-defensin-1 polymorphisms (G-20A, C-44G, G-52A and Val38Ile).

Results: There were no associations between individual polymorphisms or imputed haplotypes and rate of decline in lung function or susceptibility to infection.

Conclusion: These findings suggest that, in a white population, the defensin polymorphisms tested may not be of importance in determining who develops abnormally rapid lung function decline or is susceptible to developing lower respiratory infections.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA / genetics
  • Female
  • Gene Expression Regulation / physiology
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Linkage Disequilibrium / genetics
  • Lung / chemistry
  • Lung / physiopathology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Respiratory Function Tests
  • Respiratory Tract Infections / etiology
  • Respiratory Tract Infections / genetics
  • Smoking / adverse effects*
  • alpha-Defensins / genetics
  • alpha-Defensins / physiology*
  • beta-Defensins / genetics
  • beta-Defensins / physiology*

Substances

  • alpha-Defensins
  • beta-Defensins
  • DNA