Pre-B-cell colony-enhancing factor gene polymorphisms and risk of acute respiratory distress syndrome.
OBJECTIVE
Pre-B-cell colony-enhancing factor (PBEF) levels are elevated in bronchoalveolar lavage fluid and serum of patients with acute lung injury. There are several suspected functional polymorphisms of the corresponding PBEF gene. We hypothesized that variations in PBEF gene polymorphisms alter the risk of developing acute respiratory distress syndrome (ARDS).


METHODS
Nested case-control study.


METHODS
Tertiary academic medical center.


METHODS
We studied 375 patients with ARDS and 787 at-risk controls genotyped for the PBEF T-1001G and C-1543T polymorphisms.


METHODS
None.


RESULTS
Patients with the -1001G (variant) allele had significantly greater odds of developing ARDS than wild-type homozygotes (odds ratio, 1.35; 95% confidence interval, 1.02-1.78). Patients with the -1543T (variant) allele did not have significantly different odds of developing ARDS than wild-type homozygotes (odds ratio, 0.86; 95% confidence interval, 0.65-1.13). When analysis was stratified by ARDS risk factor, -1543T was associated with decreased odds of developing ARDS in septic shock patients (odds ratio, 0.66; 95% confidence interval, 0.45-0.97). Also, -1001G was associated with increased hazard of intensive care unit mortality, whereas -1543T was associated with decreased hazard of 28-day and 60-day ARDS mortality, as well as shorter duration of mechanical ventilation. Similar results were found in analyses of the related GC (-1001G:-1543C) and TT (-1001T:-1543T) haplotypes.


CONCLUSIONS
The PBEFT-1001G variant allele and related haplotype are associated with increased odds of developing ARDS and increased hazard of intensive care unit mortality among at-risk patients, whereas the C-1543T variant allele and related haplotype are associated with decreased odds of ARDS among patients with septic shock and better outcomes among patients with ARDS.
Bajwa
Ednan K
EK
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
Yu
Chu-Ling
CL
Gong
Michelle N
MN
Thompson
B Taylor
BT
Christiani
David C
DC
D018806:APACHE; D000483:Alleles; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D054409:Nicotinamide Phosphoribosyltransferase; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000235:genetics* / Q000401:mortality; D012307:Risk Factors; D012772:Shock, Septic / Q000150:complications
D016207:Cytokines; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human