title: Characterization of a single nucleotide polymorphism in the lipopolysaccharide binding protein and its association with sepsis.
abstract: We sought to characterize polymorphisms in the proximal coding region of the lipopolysaccharide binding protein gene and to determine whether a previously reported variant was associated with sepsis complicated by organ failure or shock after trauma. We used multiple analytical methods, including pyrosequencing, restriction fragment length polymorphism, and sequencing to characterize the proximal coding region. We also reexamined a prospective cohort of severely injured patients and healthy control individuals. The single nucleotide polymorphism at nucleotide 292 does not exist as previously reported. Instead, the adjacent nucleotide (291) was observed to be polymorphic. In 151 trauma patients, 37 (25%) developed severe sepsis, and 19 (13%) died. Thirteen of 50 (26%) C-allele carriers and 24 of 101 (24%) TT homozygotes developed severe sepsis. Unadjusted and adjusted analyses did not demonstrate any associations between genotype and severe sepsis, septic shock, or death. In conclusion, a single nucleotide polymorphism in the lipopolysaccharide binding protein coding region that was reported to exist at the 292 position and to result in an amino acid substitution actually exists at the adjacent 291 position and does not result in an amino acid substitution. Furthermore, this polymorphism does not appear to be associated with complicated sepsis after trauma.
authors.affiliation: University of Texas Southwestern Medical Center, Department of Surgery, Dallas, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Barber
authors.forename: Grant E
authors.initials: GE
authors.lastname: O'Keefe
mesh_terms: D000209:Acute-Phase Proteins; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D017931:DNA Primers / Q000032:analysis; D005260:Female; D005838:Genotype; D006801:Humans; D015601:Injury Severity Score; D007362:Intensive Care Units; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D012720:Severity of Illness Index; D016019:Survival Analysis; D014947:Wounds and Injuries / Q000150:complications; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D002352:Carrier Proteins; D017931:DNA Primers; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein