Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI, USA.
Integrated Research and Development Laboratory, Marshfield Clinic Research Institute, Marshfield, WI, USA.
Genes Immun. 2020 Aug;21(4):240-248. doi: 10.1038/s41435-020-0101-0. Epub 2020 Jun 8.
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.
宿主遗传变异可能是金黄色葡萄球菌菌血症持续时间变化的一个影响因素。我们评估了七个宿主免疫反应相关基因（TLR2、TLR4、TIRAP、IRAK4、TRAF6、NOD2 和 CISH）中 28 个单核苷酸多态性（SNP）是否与金黄色葡萄球菌菌血症持续时间有关。研究对象包括来自学术医疗中心的 158 例短期（≤4 天）和 44 例持续（>4 天）金黄色葡萄球菌菌血症患者。在单 SNP 分析中，三个 TIRAP SNP（rs655540、rs563011 和 rs8177376）的次要等位基因频率在持续菌血症中较高（P<0.05）。携带所有三个次要等位基因的单倍型也与持续菌血症相关（P=0.037）。其他四个 TIRAP SNP（rs8177342、rs4937114、rs3802813 和 rs4937115）的次要等位基因频率在短期菌血症中较高（P<0.05），包含这四个次要等位基因的单倍型与短期菌血症相关（P=0.045）。这七个 SNP 都位于调节转录的蛋白质或非编码 RNA 的结合位点。在进行多次比较调整后，所有关联均不再具有统计学意义。需要进一步研究以了解 TIRAP 和其他宿主免疫基因中的遗传变异如何影响金黄色葡萄球菌菌血症的持续时间。
