Polymorphisms in CD14, mannose-binding lectin, and Toll-like receptor-2 are associated with increased prevalence of infection in critically ill adults.
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.


METHODS
Genetic association study.


METHODS
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.


METHODS
A cohort of 252 critically ill Caucasians with systemic inflammatory response syndrome.


METHODS
DNA was extracted from discarded blood. Clinical data were gathered by retrospective chart review.


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.
Sutherland
Ainsley M
AM
University of British Columbia Critical Care Research Laboratories, James Hogg iCAPTURE Centre/St. Paul's Hospital, Vancouver, BC, Canada.
Walley
Keith R
KR
Russell
James A
JA
D000328:Adult; D001955:British Columbia / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000235:genetics*; D012306:Risk; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D018950:Lipopolysaccharide Receptors; D037601:Mannose-Binding Lectin; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors