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Title: Common Variants of TLR1 Associate with Organ Dysfunction and Sustained Pro- Inflammatory Responses during Sepsis
Author: Pino Yanes, Maria
Corrales, Almudena
Casula, Milena
Blanco, Jesús
Muriel, Arturo
Espinosa, Elena
García Bello, Miguel
Torres Martí, Antoni
Ferrer Monreal, Miquel
Zavala Zegarra, Elizabeth
Villar, Jesús
Flores, Carlos
GEN-SEP groups
Keywords: Inflamació
Malalties de l'aparell respiratori
Genètica molecular
Respiratory diseases
Molecular genetics
Issue Date: 29-Oct-2010
Publisher: Public Library of Science (PLoS)
Abstract: Background: Toll-like receptors (TLRs) are critical components for host pathogen recognition and variants in genes participating in this response influence susceptibility to infections. Recently, TLR1 gene polymorphisms have been found correlated with whole blood hyper-inflammatory responses to pathogen-associated molecules and associated with sepsis-associated multiorgan dysfunction and acute lung injury (ALI). We examined the association of common variants of TLR1 gene with sepsis-derived complications in an independent study and with serum levels for four inflammatory biomarker among septic patients. Methodology/Principal Findings: Seven tagging single nucleotide polymorphisms of the TLR1 gene were genotyped in samples from a prospective multicenter case-only study of patients with severe sepsis admitted into a network of intensive care units followed for disease severity. Interleukin (IL)-1 b, IL-6, IL-10, and C-reactive protein (CRP) serum levels were measured at study entry, at 48 h and at 7th day. Alleles -7202G and 248Ser, and the 248Ser-602Ile haplotype were associated with circulatory dysfunction among severe septic patients (0.001<=p <= 0.022), and with reduced IL-10 (0.012<= p <=0.047) and elevated CRP (0.011<= p <=0.036) serum levels during the first week of sepsis development. Additionally, the -7202GG genotype was found to be associated with hospital mortality (p =0.017) and ALI (p =0.050) in a combined analysis with European Americans, suggesting common risk effects among studies Conclusions/Significance: These results partially replicate and extend previous findings, supporting that variants of TLR1 gene are determinants of severe complications during sepsis.
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It is part of: PLoS One, 2010, vol. 10, num. 5, p. e13759
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Medicina)

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