title: Clinical relevance of TLR2, TLR4, CD14 and FcgammaRIIA gene polymorphisms in Streptococcus pneumoniae infection.
abstract: Streptococcus pneumoniae is the most common cause of community-acquired pneumonia and a major cause of morbidity and mortality throughout the world. It has been a major research priority to identify gene polymorphisms responsible for/associated with susceptibility and severity of S. pneumoniae infection to gain a better understanding of host genetic variants and their influence and clinical relevance to pneumococcal infections. In the present study, polymorphisms in several candidate genes, including TLR2-Arg/Gln753, TLR4-Asp/Gly299, TLR4-Thr/Ile399, CD14-159C/T and FcgammaRIIA-R/H131, were examined in 85 children with pneumococcal sepsis as an invasive pneumococcal disease and 409 healthy blood donors as controls. The prevalence of the TLR4-299/399 polymorphisms was significantly lower in the patient population than in controls (4 vs 11%; P<0.05; odds ratio (OR) 0.3; 95% confidence interval (CI) 0.1-1), while the prevalence of the CD14-159CC and FcgammaRIIA-R/R131 genotypes was significantly higher (35 vs 25%; P<0.05; OR 1.7; 95% CI 1-2.8 and 39 vs 21%; P<0.001; OR 2.5; 95% CI 1.4-4, respectively). Further, only 35% of patients carried either low-risk genotypes or protective genotypes in contrast to 61% of controls (P<0.0001; OR 2.8; 95% CI 1.7-4.6). We conclude that genetic variability in the TLR4, CD14 and FcgammaRIIA genes is associated with an increased risk of developing invasive disease in patients who are infected with S. pneumoniae.
authors.affiliation: Research and Development, Australian Red Cross Blood Service-Endeavour, Sydney, New South Wales, Australia. fyuan@arcbs.redcross.org.au
authors.forename: Fang Fang
authors.initials: FF
authors.lastname: Yuan
authors.forename: Katherine
authors.initials: K
authors.lastname: Marks
authors.forename: Melanie
authors.initials: M
authors.lastname: Wong
authors.forename: Sarah
authors.initials: S
authors.lastname: Watson
authors.forename: Ellen
authors.initials: E
authors.lastname: de Leon
authors.forename: Peter Bruce
authors.initials: PB
authors.lastname: McIntyre
authors.forename: John Stephen
authors.initials: JS
authors.lastname: Sullivan
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D011008:Pneumococcal Infections / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: C080568:Fc gamma receptor IIA; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4