Genetic susceptibility to invasive pneumococcal disease.

Abstract Background The pathogenesis of IPD remains unknown, especially among middle-aged individuals without risk factors (WRF). Objectives The aim of the present study was to investigate the role of single nucleotide polymorphisms (SNP) within key genes involved in innate immune response on IPD susceptibility. Methods Forty-three SNPs within 10 immunological genes were investigated in a cohort of 144 Caucasian IPD patients and 280 ethnically matched controls. Results The allele distribution of the NFKBIA rs1050851 and NFKBIE rs2282151 variants were associated with IPD susceptibility (χ 2  = 4.23, p = 0.04 and χ 2  = 5.13, p = 0.02, respectively). Additionally, the genotype distribution of NFKBIZ rs645781 (χ 2  = 8.25, p = 0.02) and IL1R1 rs3917254 (χ 2  = 6.70, p = 0.04) were also associated with IPD risk. When only IPD-WRF patients were considered; the allele distribution of IL1R1 rs2160227 (χ 2  = 5.62, p = 0.03), rs13020778 (χ 2  = 5.73, p = 0.02), rs3917267 (χ 2  = 3.72, p = 0.05) and IL4 rs2227284 (χ 2  = 3.76, p = 0.05) and the genotype distribution of IL10 rs3024509 (χ 2  = 7.70, p = 0.02), IL1R1 rs3917254 (χ 2  = 13.40, p = 0.001), NFKBIZ rs645781 (χ 2  = 13.86, p = 0.001) and rs677011 (χ 2  = 9.06, p = 0.01) variants were associated with IPD risk. Conclusions We found several associations between variants in the IL1R1, IL4, IL10, NFKBIE, NFKBIA, and NFKBIZ genes and risk of IPD. If validated, these biomarkers may help to identify people with higher risk of IPD.