期刊
JOURNAL OF INFECTIOUS DISEASES
卷 206, 期 4, 页码 495-503出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jis378
关键词
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资金
- Providence Foundation Limited
- Research Fund for the Control of Infectious Diseases (Food and Health Bureau, Hong Kong Special Administrative Region, China)
- Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Disease (Department of Health, Hong Kong Special Administrative Region, China)
Infection due to 2009 pandemic H1N1 influenza A virus (A[H1N1]pdm09) is commonly manifested as mild infection but occasionally as severe pneumonia. We hypothesized that host genetic variations may contribute to disease severity. An initially small-scale genome-wide association study guided the selection of CD55 single-nucleotide polymorphisms in 425 Chinese patients with severe (n = 177) or mild (n = 248) disease. Carriers of rs2564978 genotype T/T were significantly associated with severe infection (odds ratio, 1.75; P = .011) under a recessive model, after adjustment for clinical confounders. An allele-specific effect on CD55 expression was revealed and ascribed to a promoter indel variation, which was in complete linkage disequilibrium with rs2564978. The promoter variant with deletion exhibited significantly lower transcriptional activity. We further demonstrated that CD55 can protect respiratory epithelial cells from complement attack. Additionally, A(H1N1)pdm09 infection promoted CD55 expression. In conclusion, CD55 polymorphisms are associated with severe A(H1N1)pdm09 infection. CD55 may exert a substantial impact on the disease severity of A (H1N1)pdm09 infection.
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