Polymorphisms in the mannose binding lectin-2 gene and acute respiratory distress syndrome

Crit Care Med. 2007 Jan;35(1):48-56. doi: 10.1097/01.CCM.0000251132.10689.F3.

Abstract

Objective: The variant alleles in the mannose binding lectin-2 (MBL-2) gene have been associated with MBL deficiency and increased susceptibility to sepsis. We postulate that the variant MBL-2 genotypes are associated with increased susceptibility to and mortality in acute respiratory distress syndrome (ARDS).

Design: Nested case-control study.

Setting: Tertiary academic medical center.

Patients: Two hundred and twelve Caucasians with ARDS and 442 controls genotyped for the variant X, D, B, and C alleles of codon -221, 52, 54, and 57, respectively.

Interventions: None.

Measurements and main results: Patients homozygous for the variant codon 54B allele (54BB) had worse severity of illness on admission (p = .007), greater likelihood of septic shock (p = .04), and increased odds of ARDS (adjusted odds ratio, 6.7; 95% confidence interval, 1.5-31) when compared with heterozygotes and homozygotes for the wild-type allele. This association with ARDS was especially strong among the 311 patients with septic shock (adjusted odds ratio, 12.0; 95% confidence interval, 1.9-74). Among the patients with ARDS, the 54BB genotype was associated with more daily organ dysfunction (p = .01) and higher mortality (adjusted hazard rate, 4.0; 95% confidence interval, 1.6-10). Development of ARDS and outcomes in ARDS did not vary significantly with variant alleles of codon -221, 52, and 57, but the power to detect an effect was limited secondary to the low allele frequencies.

Conclusions: The MBL-2 codon 54BB genotype may be important in ARDS susceptibility and outcome. Additional studies are needed to confirm these findings in other populations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Boston / epidemiology
  • Case-Control Studies
  • Female
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / etiology*
  • Hospital Mortality
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mannose-Binding Lectin / genetics*
  • Middle Aged
  • Molecular Epidemiology
  • Polymorphism, Genetic / genetics*
  • Proportional Hazards Models
  • Prospective Studies
  • Respiratory Distress Syndrome / etiology*
  • Respiratory Distress Syndrome / metabolism
  • Respiratory Distress Syndrome / mortality
  • Risk Factors
  • Sepsis / complications
  • Transfusion Reaction
  • Wounds and Injuries / complications

Substances

  • MBL2 protein, human
  • Mannose-Binding Lectin