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

Michelle Ng Gong, Wei Zhou, Paige L. Williams, B. Taylor Thompson, Lucille Pothier, David C. Christiani

Research output: Contribution to journalArticle

56 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)48-56
Number of pages9
JournalCritical Care Medicine
Volume35
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

Fingerprint

Mannose-Binding Lectin
Adult Respiratory Distress Syndrome
Codon
Alleles
Genes
Genotype
Confidence Intervals
Septic Shock
Odds Ratio
Dilatation and Curettage
Mortality
Homozygote
Heterozygote
Gene Frequency
Case-Control Studies
Sepsis

Keywords

  • Acute lung injury
  • Acute respiratory failure
  • Genetic susceptibility
  • Molecular epidemiology

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Polymorphisms in the mannose binding lectin-2 gene and acute respiratory distress syndrome. / Gong, Michelle Ng; Zhou, Wei; Williams, Paige L.; Thompson, B. Taylor; Pothier, Lucille; Christiani, David C.

In: Critical Care Medicine, Vol. 35, No. 1, 01.2007, p. 48-56.

Research output: Contribution to journalArticle

Gong, Michelle Ng ; Zhou, Wei ; Williams, Paige L. ; Thompson, B. Taylor ; Pothier, Lucille ; Christiani, David C. / Polymorphisms in the mannose binding lectin-2 gene and acute respiratory distress syndrome. In: Critical Care Medicine. 2007 ; Vol. 35, No. 1. pp. 48-56.
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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.",
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AB - 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.

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