title: Impaired β-defensin expression in human skin links DEFB1 promoter polymorphisms with persistent Staphylococcus aureus nasal carriage.
abstract: BACKGROUND
  Genetically determined variation in the expression of innate defense molecules may explain differences in the propensity to be colonized with Staphylococcus aureus.
  
  
  METHODS
  We determined S. aureus nasal carriage in 603 volunteers; analyzed polymorphisms in the DEFB1 promoter at positions -52 G>A (rs1799946), -44 C>G (rs1800972), and -20 G>A (rs11362); and measured the content of human β-defensin 1 (hBD-1) and hBD-3 messenger RNA (mRNA) in 192 samples of healthy and experimentally wounded human skin.
  
  
  RESULTS
  Compared with GGG at the positions -52/-44/-20, the ACG haplotype was more common among persistent S. aureus nasal carriers (odds ratio, 1.93; 95% confidence interval [CI], 1.2-3.1; P = .006) and was associated with reduced expression of hBD-1 (GGG>ACG>GCA; P < .001) and hBD-3 (GGG>GCA>ACG; P = .04) in skin when measured 72 hours after wounding. Furthermore, a 50% decrease in hBD-1 and hBD-3 mRNA expression in wounded skin increased the odds of persistent carriage by 1.45 (95% CI, .93-2.26; P = .1) and 1.48 (95% CI, 1.01-2.17; P = .04), respectively. Adjustment for known risk factors of persistent S. aureus carriage did not substantially change the associations of both DEFB1 haplotypes and β-defensin expression with S. aureus colonization.
  
  
  CONCLUSIONS
  DEFB1 polymorphisms may promote persistent S. aureus colonization by altering β-defensin expression in keratinocytes of human skin.
authors.affiliation: Institut für Tropenmedizin,  Eberhard Karls Universität, Tübingen,  Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Nurjadi
authors.forename: Elena
authors.initials: E
authors.lastname: Herrmann
authors.forename: Isabel
authors.initials: I
authors.lastname: Hinderberger
authors.forename: Philipp
authors.initials: P
authors.lastname: Zanger
mesh_terms: D000328:Adult; D002353:Carrier State / Q000276:immunology / Q000382:microbiology*; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D056726:Genetic Association Studies; D054884:Host-Pathogen Interactions; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D009666:Nose / Q000382:microbiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000302:isolation & purification*; D055815:Young Adult; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
chemical_list: C406407:DEFB1 protein, human; C422950:DEFB103A protein, human; D023083:beta-Defensins