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Title: Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection
Authors: Herrera-Ramos, Estefanía
López-Rodríguez, Marta
Ruiz Hernández, José J. 
Horcajada, Juan P.
Borderías, Luis
Lerma, Elisabeth
Blanquer, José
Pérez-González, María C.
García-Laorden, María I.
Florido, Yanira
Mas-Bosch, Virginia
Montero, Milagro
Ferrer, José M.
Sorlí, Luisa
Vilaplana, Carlos
Rajas, Olga
Briones, Marisa
Aspa, Javier
López-Granados, Eduardo
Solé-Violán, Jordi
de Castro, Felipe R. 
Rodríguez-Gallego, Carlos 
UNESCO Clasification: 32 Ciencias médicas
2409 Genética
Keywords: H1N1 Influenza
Ozone Exposure
Definitions, et al
Issue Date: 2014
Journal: Critical Care 
Abstract: Introduction: Inherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown. Components of the innate immune response may be crucial in the first days of the infection. The collectins surfactant protein (SP)-A1, -A2, and -D and mannose-binding lectin (MBL) neutralize IAV infectivity, although only SP-A2 can establish an efficient neutralization of poorly glycosylated pandemic IAV strains.Methods: We studied the role of polymorphic variants at the genes of MBL (MBL2), SP-A1 (SFTPA1), SP-A2 (SFTPA2), and SP-D (SFTPD) in 93 patients with H1N1 pandemic 2009 (H1N1pdm) infection.Results: Multivariate analysis showed that two frequent SFTPA2 missense alleles (rs1965708-C and rs1059046-A) and the SFTPA2 haplotype 1A(0) were associated with a need for mechanical ventilation, acute respiratory failure, and acute respiratory distress syndrome. The SFTPA2 haplotype 1A(1) was a protective variant. Kaplan-Meier analysis and Cox regression also showed that diplotypes not containing the 1A(1) haplotype were associated with a significantly shorter time to ICU admission in hospitalized patients. In addition, rs1965708-C (P = 0.0007), rs1059046-A (P = 0.0007), and haplotype 1A(0) (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO2/FiO(2) ratio, whereas haplotype 1A(1) was associated with a higher PaO2/FiO(2) ratio (P = 0.001).Conclusions: Our data suggest an effect of genetic variants of SFTPA2 on the severity of H1N1pdm infection and could pave the way for a potential treatment with haplotype-specific (1A(1)) SP-A2 for future IAV pandemics.
ISSN: 1364-8535
DOI: 10.1186/cc13934
Source: Critical Care [ISSN 1364-8535],v. 18, R127, (Junio 2014)
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