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Abstract
The A(H7N9) virus strain that emerged in 2013 was associated with a high fatality rate and may become a long-term threat to public health. A(H7N9) disease incidence is disproportionate to viral exposure, suggesting that host genetic factors may significantly influence susceptibility to A(H7N9) infection. Human genome variation in conferring risk for A(H7N9) infection in Chinese populations was identified by a two-stage investigation involving 121 A(H7N9) patients and 187 healthy controls using next generation sequencing followed by functional analysis. As a result, a low frequency variant (rs189256251; P = 0.0303, OR = 3.45, 95% CI 1.05–11.35, chi-square test) and three HLA alleles (DQB1*06:01, DQA1*05:05 and C*12:02) were identified in A(H7N9) infected volunteers. In an A549 cell line carrying the rs189256251 variant CT genotype, A(H7N9) infection incidence was elevated 6.665-fold over control cells carrying the CC genotype. Serum levels of interferon alpha were significantly lower in patients with the CT genotype compared to the CC genotype (P = 0.01). The study findings of genetic predisposition to A(H7N9) in the Chinese population may be valuable in systematic investigations of A(H7N9) disease etiology.
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1 Shanghai Jiao Tong University, Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293); Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China (GRID:grid.430328.e)
2 Sun Yat-sen University, School of Public Health (Shenzhen), Shenzhen, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X)
3 Shanghai Jiao Tong University, Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293)
4 National Health Commission, National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, Beijing, China (GRID:grid.16821.3c)
5 Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China (GRID:grid.430328.e)
6 Shanghai Huangpu District Center for Disease Control and Prevention, Shanghai, China (GRID:grid.430328.e)
7 Massachusetts General Hospital and Harvard Medical School, Analytic and Translational Genetics Unit, Department of Medicine, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Broad Institute of Harvard and MIT, Cambridge, USA (GRID:grid.66859.34)
8 Anhui Medical University, Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Hefei, China (GRID:grid.186775.a) (ISNI:0000 0000 9490 772X)
9 Jinan Infectious Disease Hospital, Jinan, China (GRID:grid.186775.a)
10 National Institute for Viral Disease Control and Prevention China CDC, Beijing, China (GRID:grid.198530.6) (ISNI:0000 0000 8803 2373)
11 Sun Yat-sen University, School of Public Health (Shenzhen), Shenzhen, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X); National Health Commission, National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, Beijing, China (GRID:grid.12981.33)
12 Shanghai Jiao Tong University, Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293); Jining Medical University, Collaborative Innovation Center, Jining, China (GRID:grid.449428.7) (ISNI:0000 0004 1797 7280)