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J Infect Dis. 2012 Jun 12. [Epub ahead of print]
A functional variation in CD55 gene increases the disease severity of pandemic A(H1N1)2009 influenza infection.
Zhou J, To KK, Dong H, Cheng ZS, Lau CC, Poon VK, Fan YH, Song YQ, Tse H, Chan KH, Zheng BJ, Zhao GP, Yuen KY.
Source
Department of Microbiology.
Abstract
Pandemic H1N1 2009 [A(H1N1)pdm09] influenza is commonly manifested as mild infection but occasionally as severe pneumonia. We hypothesized host genetic variations may contribute to disease severity. An initial small scale genome wide association study guided the selection of CD55 single nucleotide polymorphisms in 425 Chinese patients with severe (n=177) and mild (n=248) disease. Carriers of rs2564978 genotype T/T were significantly associated with severe infection (OR 1.75, p=0.011) under recessive model, after adjusting the clinical confounders. 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 CD55 can protect respiratory epithelial cells from complement attack. Additionally, A(H1N1)pdm09 virus infection promoted CD55 expression. In conclusion, CD55 gene polymorphisms are associated with severe A(H1N1)pdm09 infection. CD55 may exert a substantial impact on the disease severity of A(H1N1)pdm09 infection.
PMID:
22693232
[PubMed - as supplied by publisher]
A functional variation in CD55 gene increases the disease severity of pandemic A(H1N1)2009 influenza infection.
Zhou J, To KK, Dong H, Cheng ZS, Lau CC, Poon VK, Fan YH, Song YQ, Tse H, Chan KH, Zheng BJ, Zhao GP, Yuen KY.
Source
Department of Microbiology.
Abstract
Pandemic H1N1 2009 [A(H1N1)pdm09] influenza is commonly manifested as mild infection but occasionally as severe pneumonia. We hypothesized host genetic variations may contribute to disease severity. An initial small scale genome wide association study guided the selection of CD55 single nucleotide polymorphisms in 425 Chinese patients with severe (n=177) and mild (n=248) disease. Carriers of rs2564978 genotype T/T were significantly associated with severe infection (OR 1.75, p=0.011) under recessive model, after adjusting the clinical confounders. 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 CD55 can protect respiratory epithelial cells from complement attack. Additionally, A(H1N1)pdm09 virus infection promoted CD55 expression. In conclusion, CD55 gene polymorphisms are associated with severe A(H1N1)pdm09 infection. CD55 may exert a substantial impact on the disease severity of A(H1N1)pdm09 infection.
PMID:
22693232
[PubMed - as supplied by publisher]
