Impaired β-Defensin Expression in Human Skin Links DEFB1 Promoter Polymorphisms With Persistent Staphylococcus aureus Nasal Carriage

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 beta-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 beta-defensin expression with S. aureus colonization. Conclusions. DEFB1 polymorphisms may promote persistent S. aureus colonization by altering beta-defensin expression in keratinocytes of human skin.