Association of variants in selected genes mediating host immune response with duration of Staphylococcus aureus bacteremia

• Published in: Genes and immunity Vol. 21; no. 4; pp. 240 - 248
• Main Authors: Carter, Tonia C., Ye, Zhan, Ivacic, Lynn C., Budi, Noah, Rose, Warren E., Shukla, Sanjay K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2020; Nature Publishing Group
• Subjects: 38/47; 38/77; 45/22; 631/208/721; 631/250/248; Alleles; Analysis; Bacteremia; Bacteremia - genetics; Bacteremia - immunology; Binding sites; Biomedical and Life Sciences; Biomedicine; Cancer Research; Gene Expression; Gene frequency; Genes; Genetic aspects; Genetic diversity; Genetic Predisposition to Disease; Genetic transcription; Genetic variability; Genotyping Techniques; Haplotypes; Host-Pathogen Interactions; Human Genetics; Humans; Immune response; Immunity; Immunology; Medical colleges; NOD2 protein; Penicillin; Polymorphism, Single Nucleotide; Protein binding; Proteins; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Staphylococcal Infections - genetics; Staphylococcal Infections - immunology; Staphylococcus aureus; Statistical analysis; TLR2 protein; TLR4 protein; Toll-like receptors; TRAF6 protein; Transcription
• DOI: 10.1038/s41435-020-0101-0
• ISSN: 1466-4879; 1476-5470

Host genetic variation may be a contributing factor to variability in Staphylococcus aureus bacteremia duration. We assessed whether 28 single nucleotide polymorphisms (SNPs) in seven genes ( TLR2 , TLR4 , TIRAP , IRAK4 , TRAF6, NOD2 , and CISH ) that mediate host immune response were associated with S. aureus bacteremia duration. Subjects included 158 patients with short-term (≤4 days) and 44 with persistent (>4 days) S. aureus bacteremia from an academic medical center. In single SNP analyses, the minor allele frequencies of three TIRAP SNPs (rs655540, rs563011, and rs8177376) were higher in persistent bacteremia ( P  < 0.05). A haplotype with all three minor alleles was also associated with persistent bacteremia ( P  = 0.037). The minor allele frequencies of four other TIRAP SNPs (rs8177342, rs4937114, rs3802813, and rs4937115) were higher in short-term bacteremia ( P  < 0.05), and a haplotype containing the four minor alleles was associated with short-term bacteremia ( P  = 0.045). All seven SNPs are located in binding sites for proteins or noncoding RNAs that regulate transcription. None of the associations remained statistically significant after adjustment for multiple comparisons. Further investigation is needed to understand how genetic variation in TIRAP and other host immune genes may influence the duration of S. aureus bacteremia.