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Lipopolysaccharide binding protein promoter variants influence the risk for Gram-negative bacteremia and mortality after allogeneic hematopoietic cell transplantation.
- Source :
-
Blood [Blood] 2008 Feb 15; Vol. 111 (4), pp. 2462-9. Date of Electronic Publication: 2007 Dec 03. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Adult
Case-Control Studies
Cohort Studies
DNA genetics
Female
Genotype
Hematopoietic Stem Cell Transplantation mortality
Humans
Male
Middle Aged
Neutropenia epidemiology
Polymorphism, Single Nucleotide
Retrospective Studies
Transplantation, Homologous
Acute-Phase Proteins genetics
Carrier Proteins genetics
Genetic Variation
Gram-Negative Bacterial Infections epidemiology
Hematopoietic Stem Cell Transplantation adverse effects
Membrane Glycoproteins genetics
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 111
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 18056482
- Full Text :
- https://doi.org/10.1182/blood-2007-09-101709