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Article: Identification of TMPRSS2 as a susceptibility gene for severe 2009 pandemic A(H1N1) influenza and A(H7N9) influenza

TitleIdentification of TMPRSS2 as a susceptibility gene for severe 2009 pandemic A(H1N1) influenza and A(H7N9) influenza
Authors
KeywordsTMPRSS2
A(H1N1)pdm09 influenza
A(H7N9) influenza
genetic variation
lung eQTL
Issue Date2015
Citation
Journal of Infectious Diseases, 2015, v. 212, n. 8, p. 1214-1221 How to Cite?
Abstract© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. The genetic predisposition to severe A(H1N1)2009 (A[H1N1]pdm09) influenza was evaluated in 409 patients, including 162 cases with severe infection and 247 controls with mild infection. We prioritized candidate variants based on the result of a pilot genome-wide association study and a lung expression quantitative trait locus data set. The GG genotype of rs2070788, a higher-expression variant of TMPRSS2, was a risk variant (odds ratio, 2.11; 95% confidence interval, 1.18-3.77; P =. 01) to severe A(H1N1)pdm09 influenza. A potentially functional single-nucleotide polymorphism, rs383510, accommodated in a putative regulatory region was identified to tag rs2070788. Luciferase assay results showed the putative regulatory region was a functional element, in which rs383510 regulated TMPRSS2 expression in a genotype-specific manner. Notably, rs2070788 and rs383510 were significantly associated with the susceptibility to A(H7N9) influenza in 102 patients with A(H7N9) influenza and 106 healthy controls. Therefore, we demonstrate that genetic variants with higher TMPRSS2 expression confer higher risk to severe A(H1N1)pdm09 influenza. The same variants also increase susceptibility to human A(H7N9) influenza.
Persistent Identifierhttp://hdl.handle.net/10722/222694
ISSN
2015 Impact Factor: 6.344
2015 SCImago Journal Rankings: 4.000
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheng, Zhongshan-
dc.contributor.authorZhou, Jie-
dc.contributor.authorTo, Kelvin Kai Wang-
dc.contributor.authorChu, Hin-
dc.contributor.authorLi, Cun-
dc.contributor.authorWang, Dong-
dc.contributor.authorYang, Dong-
dc.contributor.authorZheng, Shufa-
dc.contributor.authorHao, Ke-
dc.contributor.authorBossé, Yohan-
dc.contributor.authorObeidat, Ma'en-
dc.contributor.authorBrandsma, Corry Anke-
dc.contributor.authorSong, You Qiang-
dc.contributor.authorChen, Yu-
dc.contributor.authorZheng, Bo Jian-
dc.contributor.authorLi, Lanjuan-
dc.contributor.authorYuen, Kwok Yung-
dc.date.accessioned2016-01-19T03:37:01Z-
dc.date.available2016-01-19T03:37:01Z-
dc.date.issued2015-
dc.identifier.citationJournal of Infectious Diseases, 2015, v. 212, n. 8, p. 1214-1221-
dc.identifier.issn0022-1899-
dc.identifier.urihttp://hdl.handle.net/10722/222694-
dc.description.abstract© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. The genetic predisposition to severe A(H1N1)2009 (A[H1N1]pdm09) influenza was evaluated in 409 patients, including 162 cases with severe infection and 247 controls with mild infection. We prioritized candidate variants based on the result of a pilot genome-wide association study and a lung expression quantitative trait locus data set. The GG genotype of rs2070788, a higher-expression variant of TMPRSS2, was a risk variant (odds ratio, 2.11; 95% confidence interval, 1.18-3.77; P =. 01) to severe A(H1N1)pdm09 influenza. A potentially functional single-nucleotide polymorphism, rs383510, accommodated in a putative regulatory region was identified to tag rs2070788. Luciferase assay results showed the putative regulatory region was a functional element, in which rs383510 regulated TMPRSS2 expression in a genotype-specific manner. Notably, rs2070788 and rs383510 were significantly associated with the susceptibility to A(H7N9) influenza in 102 patients with A(H7N9) influenza and 106 healthy controls. Therefore, we demonstrate that genetic variants with higher TMPRSS2 expression confer higher risk to severe A(H1N1)pdm09 influenza. The same variants also increase susceptibility to human A(H7N9) influenza.-
dc.languageeng-
dc.relation.ispartofJournal of Infectious Diseases-
dc.subjectTMPRSS2-
dc.subjectA(H1N1)pdm09 influenza-
dc.subjectA(H7N9) influenza-
dc.subjectgenetic variation-
dc.subjectlung eQTL-
dc.titleIdentification of TMPRSS2 as a susceptibility gene for severe 2009 pandemic A(H1N1) influenza and A(H7N9) influenza-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1093/infdis/jiv246-
dc.identifier.pmid25904605-
dc.identifier.scopuseid_2-s2.0-84943426029-
dc.identifier.hkuros246439-
dc.identifier.volume212-
dc.identifier.issue8-
dc.identifier.spage1214-
dc.identifier.epage1221-
dc.identifier.eissn1537-6613-
dc.identifier.isiWOS:000363195400007-

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