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

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.

Figure 1

Flow diagram of study design and patient selection for case-control study. ICU, intensive care unit; ARDS, acute respiratory distress syndrome.

Figure 2

Acute Physiology and Chronic Health Evaluation (APACHE) III score on admission to the intensive care unit by genotype for the mannose binding lectin-2 codon 54 polymorphism among all 654 cases and controls. The box denotes the interquartile range (25-75%), the horizontal line in the box indicates the median, + designates the mean, and error bars indicate the 95% confidence intervals.

Figure 3

The mannose binding lectin-2 codon 54 genotype and the percentage of patients with acute respiratory distress syndrome (ARDS) with each genotype. The p value was calculated from Fisher’s exact test.

Figure 4

Estimated survival probability in the 212 patients with acute respiratory distress syndrome (ARDS) by the mannose binding lectin-2 codon 54 genotype.

Figure 5

Daily Brussels multiple organ dysfunction score for each day after development of acute respiratory distress syndrome (ARDS) for the 212 patients with ARDS after adjustment for potentially important variables such as age, trauma as a risk factor for ARDS, Acute Physiology and Chronic Health Evaluation III scores, history of treatment with corticosteroids, liver failure, transfusion, and septic shock.