title: Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection.
abstract: BACKGROUND
  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/FiO2 ratio, whereas haplotype 1A(1) was associated with a higher PaO2/FiO2 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.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Herrera-Ramos
authors.forename: Marta
authors.initials: M
authors.lastname: López-Rodríguez
authors.forename: José Juan
authors.initials: JJ
authors.lastname: Ruíz-Hernández
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Horcajada
authors.forename: Luis
authors.initials: L
authors.lastname: Borderías
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lerma
authors.forename: José
authors.initials: J
authors.lastname: Blanquer
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Pérez-González
authors.forename: María Isabel
authors.initials: MI
authors.lastname: García-Laorden
authors.forename: Yanira
authors.initials: Y
authors.lastname: Florido
authors.forename: Virginia
authors.initials: V
authors.lastname: Mas-Bosch
authors.forename: Milagro
authors.initials: M
authors.lastname: Montero
authors.forename: José María
authors.initials: JM
authors.lastname: Ferrer
authors.forename: Luisa
authors.initials: L
authors.lastname: Sorlí
authors.forename: Carlos
authors.initials: C
authors.lastname: Vilaplana
authors.forename: Olga
authors.initials: O
authors.lastname: Rajas
authors.forename: Marisa
authors.initials: M
authors.lastname: Briones
authors.forename: Javier
authors.initials: J
authors.lastname: Aspa
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Granados
authors.forename: Jordi
authors.initials: J
authors.lastname: Solé-Violán
authors.forename: Felipe Rodríguez
authors.initials: FR
authors.lastname: de Castro
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodríguez-Gallego
mesh_terms: D000328:Adult; D001794:Blood Pressure; D005260:Female; D006239:Haplotypes; D006760:Hospitalization; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics*; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; C445843:SFTPA2 protein, human