Clinical relevance of TLR2, TLR4, CD14 and FcgammaRIIA gene polymorphisms in Streptococcus pneumoniae infection.
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.
Yuan
Fang Fang
FF
Research and Development, Australian Red Cross Blood Service-Endeavour, Sydney, New South Wales, Australia. fyuan@arcbs.redcross.org.au
Marks
Katherine
K
Wong
Melanie
M
Watson
Sarah
S
de Leon
Ellen
E
McIntyre
Peter Bruce
PB
Sullivan
John Stephen
JS
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*
C080568:Fc gamma receptor IIA; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4