Exome variations of 46 innate immune genes show no association with pneumococcal meningitis susceptibility and outcome.
Variations that have previously been associated with invasive pneumococcal disease or meningitis could not be replicated.
Highest signals found were variations in CXCL1 and CARD8 for susceptibility and NOD2 and IRAK4 for outcome.
The IRAK4 rs4251552 variant shows a trend where patients with a G-allele have higher IL-6 levels in their liquor.
The pneumococcus is the most common causative pathogen of bacterial meningitis. We investigated the association of genetic variation within the coding sequences and flanking intronic regions of 46 innate immunity genes. These genes are responsible for our first line of defense during invading pathogens. In a cohort of 435 pneumococcal meningitis patients and 416 controls we found that variation within CXCL1 and CARD8 were the strongest signals associated with pneumococcal meningitis susceptibility. For disease severity we identified variations in NOD2 and IRAK4 genes to be associated with outcome. These findings can help in the understanding and treatment of pneumococcal meningitis.