IFITM3, TLR3, and CD55 Gene SNPs and Cumulative Genetic Risks for Severe Outcomes in Chinese Patients With H7N9/H1N1pdm09 Influenza
| Autor: | Bin Cao, Martin C.W. Chan, David S.C. Hui, Irene M. H. Yung, Nelson Lee, Dawei Guan, Rity Y. K. Wong, Kirsty Kwok, Yunwen Hu, Ronald C.W. Ma, Hongzhou Lu, Hui Li, Claudia H. T. Tam, Peter Horby, Zhaoqin Zhu, Paul K.S. Chan, Tin-Nok Hung, Mulei Lin, Changwen Ke |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty China Genotyping Techniques viruses SNP Single-nucleotide polymorphism outcomes Influenza A Virus H7N9 Subtype Polymorphism Single Nucleotide 03 medical and health sciences Influenza A Virus H1N1 Subtype Asian People Gene Frequency Internal medicine Genotype Genetic model Influenza Human Major Article Immunology and Allergy Medicine Humans Genetic Predisposition to Disease 1000 Genomes Project Allele frequency Genotyping Aged Proportional Hazards Models CD55 Antigens business.industry Hazard ratio virus diseases Membrane Proteins RNA-Binding Proteins Middle Aged Confidence interval Toll-Like Receptor 3 030104 developmental biology Infectious Diseases IFITM3 Female business influenza TLR3 |
| Zdroj: | The Journal of Infectious Diseases |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | Summary IFITM3 and TLR3 SNPs are associated with fatal clinical outcome of Chinese patients with avian (H7N9) or pandemic (H1N1pdm09) influenza virus infections, and the risks are cumulative. Our findings pose important public health and clinical implications in the at-risk populations. Background. We examined associations between single-nucleotide polymorphisms (SNPs) of IFITM3, TLR3, and CD55 genes and influenza clinical outcomes in Chinese. Methods. A multicenter study was conducted on 275 adult cases of avian (H7N9) and pandemic (H1N1pdm09) influenza. Host DNA was extracted from diagnostic respiratory samples; IFITM3 rs12252, TLR3 rs5743313, CD55 rs2564978, and TLR4 rs4986790/4986791 were targeted for genotyping (Sanger sequencing). The primary outcome analyzed was death. Results. IFITM3 and TLR3 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 IFITM3 CC (54.5% vs 33.2%; P = .02) and TLR3 CC (93.3% vs 76.9%; P = .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 CD55 TT genotype was linked to severity. TLR4 was nonpolymorphic. Conclusions. 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. |
| Databáze: | OpenAIRE |
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