title: Association of mannose-binding lectin 2 gene polymorphisms with persistent Staphylococcus aureus bacteremia.
abstract: OBJECTIVE
  Mannose-binding lectin (MBL) is an important component of innate immunity. Structural and promoter polymorphisms in the MBL2 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 MBL2 polymorphisms with persistent Staphylococcus aureus bacteremia (SAB) in adult Korean patients.
  
  
  METHODS
  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 H/L, X/Y, and P/Q) and exon 1 (alleles A/B, A/C, and A/D) of the MBL2 gene and measured serum MBL concentrations. We also compared MBL2 genotypes between SAB patients and healthy people.
  
  
  RESULTS
  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 (P = 0.019 and P = 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; P = 0.003), methicillin resistance (aOR, 4.10; 95% CI, 3.19-29.57; P = 0.025), and low/deficient MBL-producing genotypes (aOR, 7.64; 95% CI, 4.12-63.39; P = 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; P = 0.040).
  
  
  CONCLUSIONS
  This is the first demonstration of an association of low MBL levels and MBL2 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.
authors.affiliation: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Center for Antimicrobial Resistance and Microbial Genetics, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Yong Pil
authors.initials: YP
authors.lastname: Chong
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
authors.forename: Ki-Ho
authors.initials: KH
authors.lastname: Park
authors.affiliation: Center for Antimicrobial Resistance and Microbial Genetics, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kim
authors.affiliation: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung-Han
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang-Oh
authors.initials: SO
authors.lastname: Lee
authors.affiliation: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Center for Antimicrobial Resistance and Microbial Genetics, University of Ulsan College of Medicine, Seoul, Republic of Korea; Asan Institute of Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Woo
authors.affiliation: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Center for Antimicrobial Resistance and Microbial Genetics, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Yang Soo
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000368:Aged; D016470:Bacteremia / Q000150:complications / Q000235:genetics* / Q000382:microbiology; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013203:Staphylococcal Infections / Q000150:complications / Q000235:genetics* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000502:physiology*
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin