Association of mannose-binding lectin-2 genotype and serum levels with prognosis of sepsis

Crit Care. 2009;13(6):R176. doi: 10.1186/cc8157. Epub 2009 Nov 5.

Abstract

Introduction: Individuals deficient in mannose-binding lectin (MBL), an important component of the innate immune system, show increased susceptibility to infection. We investigated whether polymorphisms in the MBL2 gene and the serum level are associated with the severity and prognosis of sepsis.

Methods: A total of 266 patients with sepsis and 398 healthy controls were enrolled. We analyzed the three single nucleotide polymorphisms (Gly54Asp, -550, and +4) in the MBL2 gene. Serum samples collected on day 1 were analyzed for the levels of MBL.

Results: Patients who were heterozygous (A/B) or homozygous (B/B) at codon 54 (adjusted odds ratio (OR), 0.370; 95% confidence interval (CI), 0.207-0.661, P = 0.001) and who were heterozygous (H/L) or homozygous (L/L) at -550 (adjusted OR, 0.476; 95% CI, 0.249-0.910, P = 0.025) were less likely to have septic shock in the sepsis group. Using Cox regression analysis for 28-day mortality, an MBL level > or = 1.3 microg/mL showed significantly lower 28-day mortality (P = 0.020; hazard ratio, 0.571; 95% CI, 0.355-0.916) in the septic shock group.

Conclusions: Homozygosity at codons 54 (A/A) and -550 (H/H) appears to be associated with the severity, but not the outcome, of sepsis, whereas a low MBL level may be an independent risk factor for mortality. These findings suggest that the genotype and serum level for MBL2 may have different clinical implications.

MeSH terms

  • Aged
  • Amino Acid Substitution
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Mannose-Binding Lectin / blood*
  • Mannose-Binding Lectin / deficiency
  • Mannose-Binding Lectin / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Reference Values
  • Retrospective Studies
  • Sepsis / blood*
  • Sepsis / genetics*
  • Shock, Septic / blood
  • Shock, Septic / genetics
  • Treatment Outcome

Substances

  • DNA Primers
  • MBL2 protein, human
  • Mannose-Binding Lectin