Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia : a prospective, observational, genetic study
García Laorden, M. Isabel (Hospital Universitario de Gran Canaria Dr. Negrín)
Rodríguez de Castro, Felipe (Hospital Universitario de Gran Canaria Dr. Negrín)
Solé Violán, Jordi (Hospital Universitario de Gran Canaria Dr. Negrín)
Rajas, Olga (Hospital Universitario de la Princesa (Madrid))
Blanquer, José (Hospital Clínic Universitari (València))
Borderías, Luis (Hospital General Universitario San Jorge (Osca, Aragó))
Aspa, Javier (Hospital Universitario de la Princesa (Madrid))
Briones, M. Luisa (Hospital Clínic Universitari (València))
Saavedra, Pedro (Universidad de Las Palmas de Gran Canaria)
Marcos Ramos, J. Alberto (Hospital Dr. José Molina Orosa (Lanzarote))
González Quevedo, Nereida (Hospital Universitario de Gran Canaria Dr. Negrín)
Sologuren, Ithaisa (Hospital Universitario de Gran Canaria Dr. Negrín)
Herrera-Ramos, Estefanía (Hospital Universitario de Gran Canaria Dr. Negrín)
Ferrer, José M. (Hospital Universitario de Gran Canaria Dr. Negrín)
Rello, Jordi (Universitat Autònoma de Barcelona. Departament de Medicina)
Rodríguez Gallego, Carlos (Hospital Universitario de Gran Canaria Dr. Negrín)

Fecha:	2011
Resumen:	Introduction: Genetic variability of the pulmonary surfactant proteins A and D may affect clearance of microorganisms and the extent of the inflammatory response. The genes of these collectins (SFTPA1, SFTPA2 and SFTPD) are located in a cluster at 10q21-24. The objective of this study was to evaluate the existence of linkage disequilibrium (LD) among these genes, and the association of variability at these genes with susceptibility and outcome of community-acquired pneumonia (CAP). We also studied the effect of genetic variability on SP-D serum levels. Methods: Seven non-synonymous polymorphisms of SFTPA1, SFTPA2 and SFTPD were analyzed. For susceptibility, 682 CAP patients and 769 controls were studied in a case-control study. Severity and outcome were evaluated in a prospective study. Haplotypes were inferred and LD was characterized. SP-D serum levels were measured in healthy controls. Results: The SFTPD aa11-C allele was significantly associated with lower SP-D serum levels, in a dose-dependent manner. We observed the existence of LD among the studied genes. Haplotypes SFTPA1 6A2 (P = 0. 0009, odds ration (OR) = 0. 78), SFTPA2 1A0 (P = 0. 002, OR = 0. 79), SFTPA1-SFTPA2 6A2-1A0 (P = 0. 0005, OR = 0. 77), and SFTPD-SFTPA1-SFTPA2 C-6A2-1A0 (P = 0. 00001, OR = 0. 62) were underrepresented in patients, whereas haplotypes SFTPA2 1A10 (P = 0. 00007, OR = 6. 58) and SFTPA1-SFTPA2 6A3-1A (P = 0. 0007, OR = 3. 92) were overrepresented. Similar results were observed in CAP due to pneumococcus, though no significant differences were now observed after Bonferroni corrections. 1A10 and 6A-1A were associated with higher 28-day and 90-day mortality, and with multi-organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) respectively. SFTPD aa11-C allele was associated with development of MODS and ARDS. Conclusions: Our study indicates that missense single nucleotide polymorphisms and haplotypes of SFTPA1, SFTPA2 and SFTPD are associated with susceptibility to CAP, and that several haplotypes also influence severity and outcome of CAP.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; Versió publicada
Publicado en:	Critical Care, Vol. 15, Núm. R57 (February 2011) , p. 1-12, ISSN 1466-609X

DOI: 10.1186/cc10030
PMID: 21310059

12 p, 1.1 MB

Additional file 1 8 p, 27.4 KB

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