Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia: A prospective, observational, genetic study
Author
García-Laorden, María Isabel; Rodríguez De Castro, Felipe; Solé-Violán, Jordi; Rajas, Olga; Blanquer, José M.; Borderías, Luís; Aspa Marco, Francisco Javier; Briones, María Luisa; Saavedra Santana, P.; Marcos-Ramos, José Alberto; González-Quevedo, Nereida; Sologuren, Ithaisa; Herrera-Ramos, Estefanía; Ferrer, José M Escribano; Rello, Jordi; Rodríguez-Gallego, CarlosEntity
UAM. Departamento de MedicinaPublisher
BioMed CentralDate
2011-02-10Citation
10.1186/cc10030
Critical Care 15 (2011): 57
ISSN
1364-8535DOI
10.1186/cc10030Funded by
The present study was supported by grants from “Fondo de Investigaciones Sanitarias”, Ministerio de Sanidad (FIS 02/1620, 04/1190 and 06/1031) with the funding of European Regional Development Fund- European Social Fund (FEDER-FSE); “Sociedad Española de Neumología y Cirugía Torácica” (SEPAR); RedRespira-ISCIII-RTIC-03/11; FUNCIS, Gobierno de Canarias (04/09); NGQ was supported by FUNCIS (INREDCAN 5/06), MIGL by FUNCIS (Proyecto Biorregion 2006) and EHR by a grant from Universidad de Las Palmas de Gran CanariaEditor's Version
http://ccforum.com/content/15/1/R57Subjects
Surfactant proteins; SFTPA1, SFTPA2 and SFTPD; CAP; MedicinaRights
© 2011 García-Laorden et al.; licensee BioMed Central Ltd.Abstract
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.
Files in this item
Google Scholar:García-Laorden, María Isabel
-
Rodríguez De Castro, Felipe
-
Solé-Violán, Jordi
-
Rajas, Olga
-
Blanquer, José M.
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Borderías, Luís
-
Aspa Marco, Francisco Javier
-
Briones, María Luisa
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Saavedra Santana, P.
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Marcos-Ramos, José Alberto
-
González-Quevedo, Nereida
-
Sologuren, Ithaisa
-
Herrera-Ramos, Estefanía
-
Ferrer, José M Escribano
-
Rello, Jordi
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Rodríguez-Gallego, Carlos
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