Published ahead of print on February 13, 2003, doi:10.1164/rccm.200209-1064OC Am. J. Respir. Crit. Care Med., Volume 167, Number 10, May 2003, 1316-1320 A more recent version of this article appeared on May 15, 2003
Submitted on September 26, 2002 Characterization of a SNP in the Lipopolysaccharide Binding Protein and its Association with SepsisRobert C Barber1 and Grant E O'Keefe2*1 Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA, 2 Surgery, HMC Division, University of Washington and Harborview Medical Center, Seattle, WA, USA * To whom correspondence should be addressed. E-mail: gokeefe{at}u.washington.edu.
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 utilized multiple analytical methodologies, 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. Key words: severe sepsis, genotype
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