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


METHODS
Nested case-control study.


METHODS
Tertiary academic medical center.


METHODS
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.


METHODS
None.


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.
Gong
Michelle N
MN
Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
Zhou
Wei
W
Williams
Paige L
PL
Thompson
B Taylor
BT
Pothier
Lucille
L
Christiani
David C
DC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001900:Boston / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000209:etiology*; D017052:Hospital Mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D017720:Molecular Epidemiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000378:metabolism / Q000401:mortality; D012307:Risk Factors; D018805:Sepsis / Q000150:complications; D065227:Transfusion Reaction; D014947:Wounds and Injuries / Q000150:complications
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin