Low-Copy Number Polymorphism in DEFA1/DEFA3 Is Associated with Susceptibility to Hospital-Acquired Infections in Critically Ill Patients

DEFA1/DEFA3, genes encoding human neutrophil peptides (HNP) 1–3, display wide-ranging copy number variations (CNVs) and is functionally associated with innate immunity and infections. To identify potential associations between DEFA1/DEFA3 CNV and hospital-acquired infections (HAIs), we enrolled 106 patients with HAIs and 109 controls in the intensive care unit (ICU) and examined their DEFA1/DEFA3 CNVs. DEFA1/DEFA3 copy number ranged from 2 to 16 per diploid genome in all 215 critically ill patients, with a median of 7 copies. In HAIs, DEFA1/DEFA3 CNV varied from 2 to 12 with a median of 6, which was significantly lower than that in controls (2 to 16 with a median of 8, p = 0.017). Patients with lower DEFA1/DEFA3 copy number (CNV < 7) were far more common in HAIs than in controls (52.8% in HAIs versus 35.8% in controls; p = 0.014; OR, 2.010; 95% CI, 1.164–3.472). The area under the receiver operating characteristic (AUROC) of DEFA1/DEFA3 CNV combined with clinical characteristics to predict the incidence of HAIs was 0.763 (95% CI 0.700–0.827), showing strong predictive ability. Therefore, lower DEFA1/DEFA3 copy number contributes to higher susceptibility to HAIs in critically ill patients, and DEFA1/DEFA3 CNV is a significant hereditary factor for predicting HAIs.