Polymorphisms in themannose binding lectin-2gene... : Critical Care Medicine (original) (raw)

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

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

Critical Care Medicine

(

)

January 2007

| DOI: 10.1097/01.CCM.0000251132.10689.F3

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.