Genetic susceptibility to invasive pneumococcal disease

• Published in: Infection, genetics and evolution Vol. 59; pp. 126 - 131
• Main Authors: Sangil, Anna, Arranz, María J., Güerri-Fernández, Roberto, Pérez, Maite, Monzón, Helena, Payeras, Antoni, Andrés, Marta, Torviso, Jorge, Ibañez, Laura, Garau, Javier, Calbo, Esther
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2018
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; alleles; bacterial infections; biomarkers; Case-Control Studies; Cytokines - genetics; Female; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genetic susceptibility; genotype; Humans; Immunity, Innate - genetics; Innate immune response; innate immunity; interleukin-10; interleukin-4; Invasive pneumococcal disease; Male; Middle Aged; pathogenesis; patients; people; Pneumococcal Infections - epidemiology; Pneumococcal Infections - genetics; Pneumonia; Polymorphism, Single Nucleotide - genetics; risk factors; S. pneumoniae; single nucleotide polymorphism; Streptococcus pneumoniae; Young Adult; Iκb; Pneumonia; HIV; NFκb; SNP; Invasive pneumococcal disease; WRF; IL-1R; IPD; COPD; S. pneumoniae; Genetic susceptibility; Innate immune response
• ISSN: 1567-1348; 1567-7257; 1567-7257
• DOI: 10.1016/j.meegid.2018.01.024

The pathogenesis of IPD remains unknown, especially among middle-aged individuals without risk factors (WRF). 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. Forty-three SNPs within 10 immunological genes were investigated in a cohort of 144 Caucasian IPD patients and 280 ethnically matched controls. The allele distribution of the NFKBIA rs1050851 and NFKBIE rs2282151 variants were associated with IPD susceptibility (χ2 = 4.23, p = 0.04 and χ2 = 5.13, p = 0.02, respectively). Additionally, the genotype distribution of NFKBIZ rs645781 (χ2 = 8.25, p = 0.02) and IL1R1 rs3917254 (χ2 = 6.70, p = 0.04) were also associated with IPD risk. When only IPD-WRF patients were considered; the allele distribution of IL1R1 rs2160227 (χ2 = 5.62, p = 0.03), rs13020778 (χ2 = 5.73, p = 0.02), rs3917267 (χ2 = 3.72, p = 0.05) and IL4 rs2227284 (χ2 = 3.76, p = 0.05) and the genotype distribution of IL10 rs3024509 (χ2 = 7.70, p = 0.02), IL1R1 rs3917254 (χ2 = 13.40, p = 0.001), NFKBIZ rs645781 (χ2 = 13.86, p = 0.001) and rs677011 (χ2 = 9.06, p = 0.01) variants were associated with IPD risk. 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. •We investigate the role of single nucleotide polymorphisms (SNP) within key genes involved in innate immune response on Invasive Pneumococcal Disease (IPD).•Forty-three SNPs within 10 immunological genes were investigated in a cohort of 144 Caucasian IPD patients and 280 ethnically matched controls.•We found 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.