title: Contribution of alpha- and beta-defensins to lung function decline and infection in smokers: an association study.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Vancouver, Canada. aw2264@columbia.edu
authors.forename: Alison M
authors.initials: AM
authors.lastname: Wallace
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: He
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Burkett
authors.forename: Jian
authors.initials: J
authors.lastname: Ruan
authors.forename: John E
authors.initials: JE
authors.lastname: Connett
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Anthonisen
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sandford
mesh_terms: D000328:Adult; D004247:DNA / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008168:Lung / Q000737:chemistry / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D012129:Respiratory Function Tests; D012141:Respiratory Tract Infections / Q000209:etiology / Q000235:genetics; D012907:Smoking / Q000009:adverse effects*; D023084:alpha-Defensins / Q000235:genetics / Q000502:physiology*; D023083:beta-Defensins / Q000235:genetics / Q000502:physiology*
chemical_list: D023084:alpha-Defensins; D023083:beta-Defensins; D004247:DNA