Characterization of a Single Nucleotide Polymorphism in the Lipopolysaccharide Binding Protein and Its Association with Sepsis

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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.