| Summary: | <p><b>Background.</b> We examined associations between single-nucleotide polymorphisms (SNPs) of <i>IFITM3</i>, <i>TLR3</i>, and <i>CD55</i> genes and influenza clinical outcomes in Chinese.</p> <p><b>Methods.</b> A multicenter study was conducted on 275 adult cases of avian (H7N9) and pandemic (H1N1<sub>pdm09</sub>) influenza. Host DNA was extracted from diagnostic respiratory samples; <i>IFITM3</i> rs12252, <i>TLR3</i> rs5743313, <i>CD55</i> rs2564978, and <i>TLR4</i> rs4986790/4986791 were targeted for genotyping (Sanger sequencing). The primary outcome analyzed was death.</p> <p><b>Results.</b> <i>IFITM3</i> and <i>TLR3</i> SNPs were in Hardy–Weinberg equilibrium; their allele frequencies (IFITM3/C-allele 0.56, TLR3/C-allele 0.88) were comparable to 1000 Genomes Han Chinese data. We found over-representation of homozygous <i>IFITM3</i> CC (54.5% vs 33.2%; <i>P</i> = .02) and <i>TLR3</i> CC (93.3% vs 76.9%; <i>P</i> = .04) genotypes among fatal cases. Recessive genetic models showed their significant independent associations with higher death risks (adjusted hazard ratio [aHR] 2.78, 95% confidence interval [CI] 1.29–6.02, and aHR 4.85, 95% CI 1.11−21.06, respectively). Cumulative effects were found (aHR 3.53, 95% CI 1.64−7.59 per risk genotype; aHR 9.99, 95% CI 1.27−78.59 with both). Results were consistent for each influenza subtype and other severity indicators. The <i>CD55</i> TT genotype was linked to severity. <i>TLR4</i> was nonpolymorphic.</p> <p><b>Conclusions.</b> Host genetic factors may influence clinical outcomes of avian and pandemic influenza infections. Such findings have important implications on disease burden and patient care in at-risk populations.</p>
|
|---|