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.
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.
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