IFITM3, TLR3, and CD55 gene SNPs and cumulative genetic risks for severe outcomes in Chinese patients with H7N9/H1N1pdm09 influenza
<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 multi...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2017
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| _version_ | 1797058118177259520 |
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| author | Lee, N Cao, B Ke, C Lu, H Hu, Y Tam, H Ma, C Guan, D Zhu, Z Li, H Mulei, L Wong, R Yung, I Hung, T Kwok, K Horby, P Hui, S Chan, C Chan, K |
| author_facet | Lee, N Cao, B Ke, C Lu, H Hu, Y Tam, H Ma, C Guan, D Zhu, Z Li, H Mulei, L Wong, R Yung, I Hung, T Kwok, K Horby, P Hui, S Chan, C Chan, K |
| author_sort | Lee, N |
| collection | OXFORD |
| description | <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> |
| first_indexed | 2024-03-06T19:46:00Z |
| format | Journal article |
| id | oxford-uuid:2250ae57-bc8f-4390-9443-5a9e96955ee4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:46:00Z |
| publishDate | 2017 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:2250ae57-bc8f-4390-9443-5a9e96955ee42022-03-26T11:38:08ZIFITM3, TLR3, and CD55 gene SNPs and cumulative genetic risks for severe outcomes in Chinese patients with H7N9/H1N1pdm09 influenzaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2250ae57-bc8f-4390-9443-5a9e96955ee4EnglishSymplectic Elements at OxfordOxford University Press2017Lee, NCao, BKe, CLu, HHu, YTam, HMa, CGuan, DZhu, ZLi, HMulei, LWong, RYung, IHung, TKwok, KHorby, PHui, SChan, CChan, K <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> |
| spellingShingle | Lee, N Cao, B Ke, C Lu, H Hu, Y Tam, H Ma, C Guan, D Zhu, Z Li, H Mulei, L Wong, R Yung, I Hung, T Kwok, K Horby, P Hui, S Chan, C Chan, K IFITM3, TLR3, and CD55 gene SNPs and cumulative genetic risks for severe outcomes in Chinese patients with H7N9/H1N1pdm09 influenza |
| title | IFITM3, TLR3, and CD55 gene SNPs and cumulative genetic risks for severe outcomes in Chinese patients with H7N9/H1N1pdm09 influenza |
| title_full | IFITM3, TLR3, and CD55 gene SNPs and cumulative genetic risks for severe outcomes in Chinese patients with H7N9/H1N1pdm09 influenza |
| title_fullStr | IFITM3, TLR3, and CD55 gene SNPs and cumulative genetic risks for severe outcomes in Chinese patients with H7N9/H1N1pdm09 influenza |
| title_full_unstemmed | IFITM3, TLR3, and CD55 gene SNPs and cumulative genetic risks for severe outcomes in Chinese patients with H7N9/H1N1pdm09 influenza |
| title_short | IFITM3, TLR3, and CD55 gene SNPs and cumulative genetic risks for severe outcomes in Chinese patients with H7N9/H1N1pdm09 influenza |
| title_sort | ifitm3 tlr3 and cd55 gene snps and cumulative genetic risks for severe outcomes in chinese patients with h7n9 h1n1pdm09 influenza |
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