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Polymorphisms In CD14, Mannose-binding Lectin, And Toll-like Receptor-2 Are Associated With Increased Prevalence Of Infection In Critically Ill Adults*

Ainsley M. Sutherland, K. Walley, J. Russell
Published 2005 · Medicine

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Objective:To test for the association of single nucleotide polymorphisms of the innate immunity receptors cluster of differentiation (CD)-14, mannose-binding lectin, and Toll-like receptor-2 with clinical phenotype in critically ill patients with systemic inflammatory response syndrome. Design:Genetic association study. Setting:Tertiary care mixed medical-surgery intensive care unit at St. Paul's Hospital, Vancouver, BC, a teaching hospital associated with the University of British Columbia. Patients:A cohort of 252 critically ill Caucasians with systemic inflammatory response syndrome. Interventions:DNA was extracted from discarded blood. Clinical data were gathered by retrospective chart review. Measurements and Main Results:C-159T CD14, the X/Y and B, C, and D polymorphisms of mannose-binding lectin, and T-16933A Toll-like receptor-2 were genotyped using polymerase chain reaction-restriction fragment length polymorphism. We tested for association of genotype with prevalence of positive bacterial cultures, type of organism (Gram-positive, Gram-negative, other), sepsis and septic shock at admission to the intensive care unit, and 28-day survival. CD14 −159TT was associated with increased prevalence of positive bacterial cultures and with Gram-negative bacteria. Mannose-binding lectin haplotype pairs XO/O and O/O were also associated with increased prevalence of positive bacterial cultures but not with a specific organism class. Toll-like receptor-2 −16933AA was associated with increased prevalence of sepsis and with Gram-positive bacteria. In contrast, the polymorphisms were not associated with increased prevalence of septic shock or altered 28-day survival. Conclusions:Single nucleotide polymorphisms in CD14, mannose-binding lectin, and Toll-like receptor-2 are associated with increased prevalence of positive bacterial cultures and sepsis but not with altered prevalence of septic shock or decreased 28-day survival. Furthermore, CD14 single nucleotide polymorphisms were associated with Gram-negative bacteria and Toll-like receptor-2 with Gram-positive bacteria, whereas mannose-binding lectin was not associated with a particular organism class. Thus, single nucleotide polymorphisms in innate immunity receptors may alter recognition and clearance of bacteria without changing outcomes of critically ill adults with systemic inflammatory response syndrome.
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