Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/46586
Title: Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia: a prospective, observational, genetic study
Authors: García-Laorden, M. Isabel
Rodríguez de Castro, Felipe 
Solé-Violán, Jordi
Rajas, Olga
Blanquer, José
Borderías, Luis
Aspa, Javier
Briones, M. Luisa
Saavedra, Pedro
Marcos-Ramos, J. Alberto
González-Quevedo, Nereida
Sologuren, Ithaisa
Herrera-Ramos, Estefanía
Ferrer, José M.
Rello, Jordi
Rodríguez-Gallego, Carlos 
UNESCO Clasification: 32 Ciencias médicas
230204 Genética bioquímica
Keywords: Human Sp-A
Respiratory Syncytial Virus
In-Vivo
Infectious-Diseases
Human Sp-A1, et al
Issue Date: 2011
Journal: Critical Care 
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 6A(2) (P = 0.0009, odds ration (OR) = 0.78), SFTPA2 1A(0) (P = 0.002, OR = 0.79), SFTPA1-SFTPA2 6A(2) 1A(0) (P = 0.0005, OR = 0.77), and SFTPD-SFTPA1-SFTPA2 C-6A(2) 1A(0) (P = 0.00001, OR = 0.62) were underrepresented in patients, whereas haplotypes SFTPA2 1A(10) (P = 0.00007, OR = 6.58) and SFTPA1-SFTPA2 6A(3)-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. 1A(10) 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.
URI: http://hdl.handle.net/10553/46586
ISSN: 1466-609X
DOI: 10.1186/cc10030
Source: Critical Care [ISSN 1466-609X], v. 15 (R57), (Febrero 2011)
Appears in Collections:Artículos
Thumbnail
pdf
Adobe PDF (1,03 MB)
Show full item record

SCOPUSTM   
Citations

37
checked on Mar 24, 2024

WEB OF SCIENCETM
Citations

34
checked on Feb 25, 2024

Page view(s)

95
checked on Mar 16, 2024

Download(s)

49
checked on Mar 16, 2024

Google ScholarTM

Check

Altmetric


Share



Export metadata



Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.