Lipopolysaccharide binding protein promoter variants influence the risk for Gram-negative bacteremia and mortality after allogeneic hematopoietic cell transplantation.
Lipopolysaccharide binding protein (LBP) function is dependent on circulating LBP levels. Disturbance of LBP transcription regulation may influence the risk for clinical events. In a nested case-control study using a single nucleotide polymorphism haplotype tagging (tagSNP) approach, we assessed whether genetic variation in the LBP gene influences the risk for Gram-negative (GN) bacteremia after allogeneic hematopoietic cell transplantation (HCT), then validated the association in a prospective cohort by correlating genetic variation with basal serum LBP levels and mortality. Presence of the tagSNP 6878 C allele among patients was associated with a 2-fold higher risk for GN bacteremia (odds ratio = 2.15; 95% confidence interval [CI], 1.31-3.52, P = .002). TagSNP 6878 was in strong linkage disequilibrium with 3 SNPs in the LBP promoter, one of which was SNP 1683 (r(2) = 0.8), located in a CAAT box that regulates LBP promoter efficiency. SNP 1683 was associated with higher median basal serum LBP levels (TT 8.07 microg/mL; TC 10.40 microg/mL; CC 17.39 microg/mL; P = .002), and a 5-fold increase in GN bacteremia related mortality after HCT (hazard ratio = 4.83; 95% CI, 1.38-16.75, P = .013). These data suggest that transcriptional regulation of the LBP gene contributes to the risk for developing GN bacteremia and death after HCT.
Chien
Jason W
JW
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. jchien@fhcrc.org
Boeckh
Michael J
MJ
Hansen
John A
JA
Clark
Joan G
JG
D000209:Acute-Phase Proteins / Q000235:genetics*; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D016905:Gram-Negative Bacterial Infections / Q000453:epidemiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009503:Neutropenia / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D014158:Transcription, Genetic; D014184:Transplantation, Homologous; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D004247:DNA; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein