Abstract | OBJECTIVE: DESIGN: Prospectively enrolled case-control study of adults with severe sepsis. SETTING: A network of intensive care units. PATIENTS: We enrolled 175 patients meeting international definition criteria for severe sepsis and 357 population-based controls for comparison. INTERVENTIONS: Genotyping of the LBP gene was performed and disease association was tested. Serum lipopolysaccharide-binding protein levels were measured in patients and related to genetic variants. MEASUREMENTS AND MAIN RESULTS: A haplotype window analysis revealed that a common 4-SNP risk haplotype from the 5'-flanking region of the LBP gene, comprising positions -1978 to -763 from the transcription start site, was strongly associated with susceptibility to severe sepsis. Risk haplotype homozygous carriers had an increased risk for severe sepsis (odds ratio = 2.21; 95% confidence interval = 1.39-3.51; unadjusted p < .001; adjusted p < .025). Mean serum lipopolysaccharide-binding protein levels from inclusion to 7th day were significantly higher in homozygous carriers patients (130.1 [102.9-164.5] and 98.9 [79.7-122.8] microg/mL, respectively) than in noncarriers (101.6 [87.9-117.5] and 58.7 [51.4-67.2] microg/mL, respectively) (p = .046). CONCLUSIONS:
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Authors | Carlos Flores, Lina Pérez-Méndez, Nicole Maca-Meyer, Arturo Muriel, Elena Espinosa, Jesús Blanco, Rubén Sangüesa, Mercedes Muros, Joe G N Garcia, Jesús Villar, GRECIA and Gen-SEP groups |
Journal | Critical care medicine
(Crit Care Med)
Vol. 37
Issue 10
Pg. 2759-66
(Oct 2009)
ISSN: 1530-0293 [Electronic] United States |
PMID | 19707138
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Carrier Proteins
- Membrane Proteins
- RAPH1 protein, human
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Topics |
- APACHE
- Aged
- Alleles
- Carrier Proteins
(blood, genetics)
- Female
- Gene Frequency
- Genetic Carrier Screening
- Genetic Predisposition to Disease
(genetics)
- Genetic Testing
- Genotype
- Haplotypes
- Hospital Mortality
- Humans
- Intensive Care Units
- Linkage Disequilibrium
- Longitudinal Studies
- Male
- Membrane Proteins
(blood, genetics)
- Middle Aged
- Polymorphism, Single Nucleotide
(genetics)
- Sepsis
(blood, diagnosis, genetics, mortality)
- Survival Analysis
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