Clinical relevance of TLR2, TLR4, CD14 and FcγRIIA 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 FcγRIIA‐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 FcγRIIA‐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 FcγRIIA genes is associated with an increased risk of developing invasive disease in patients who are infected with S. pneumoniae .