Association of Mannose-Binding Lectin 2 Gene Polymorphisms with Persistent <i>Staphylococcus aureus</i> Bacteremia

<div><p>Objectives</p><p>Mannose-binding lectin (MBL) is an important component of innate immunity. Structural and promoter polymorphisms in the <i>MBL2</i> gene that are responsible for low MBL levels are associated with susceptibility to infectious diseases. The objective of this study was to investigate the association of serum MBL levels and <i>MBL2</i> polymorphisms with persistent <i>Staphylococcus aureus</i> bacteremia (SAB) in adult Korean patients.</p><p>Methods</p><p>We conducted a case-control study nested in a prospective cohort of patients with SAB. The study compared 41 patients with persistent bacteremia (≥7 days) and 46 patients with resolving bacteremia (<3 days). In each subject, we genotyped six single-nucleotide polymorphisms in the promoter region (alleles <i>H/L</i>, <i>X/Y</i>, and <i>P/Q</i>) and exon 1 (alleles <i>A/B</i>, <i>A/C</i>, and <i>A/D</i>) of the <i>MBL2</i> gene and measured serum MBL concentrations. We also compared <i>MBL2</i> genotypes between SAB patients and healthy people.</p><p>Results</p><p>Patients with persistent bacteremia were significantly more likely to have low/deficient MBL-producing genotypes and resultant low serum MBL levels, than were patients with resolving bacteremia (<i>P</i> = 0.019 and <i>P</i> = 0.012, respectively). Independent risk factors for persistent bacteremia were metastatic infection (adjusted odds ratio [aOR], 34.7; 95% confidence interval [CI], 12.83–196.37; <i>P</i> = 0.003), methicillin resistance (aOR, 4.10; 95% CI, 3.19–29.57; <i>P</i> = 0.025), and low/deficient MBL-producing genotypes (aOR, 7.64; 95% CI, 4.12–63.39; <i>P</i> = 0.003). Such genotypes were significantly more common in patients with persistent bacteremia than in healthy people (OR, 2.09; 95% CI, 1.03–4.26; <i>P</i> = 0.040).</p><p>Conclusions</p><p>This is the first demonstration of an association of low MBL levels and <i>MBL2</i> polymorphisms responsible for low or deficient MBL levels with persistent SAB. A combination of factors, including clinical and microbiological characteristics and host defense factors such as MBL levels, may together contribute to the development of persistent SAB.</p>