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Open Access 01-12-2010 | Research article

Genetic variants in the TIRAP gene are associated with increased risk of sepsis-associated acute lung injury

Authors: Zhenju Song, Chaoyang Tong, Zhan Sun, Yao Shen, Chenling Yao, Jinjun Jiang, Jun Yin, Lei Gao, Yuanlin Song, Chunxue Bai

Published in: BMC Medical Genetics | Issue 1/2010

Abstract

Background

Toll like receptors (TLRs) signaling pathways, including the adaptor protein Mal encoded by the TIRAP gene, play a central role in the development of acute lung injury (ALI). Recently, the TIRAP variants have been described association with susceptibility to inflammatory diseases. The aim of this study was to investigate whether genetic variants in TIRAP are associated with the development of ALI.

Methods

A case-control collection from Han Chinese of 298 healthy subjects, 278 sepsis-associated ALI and 288 sepsis alone patients were included. Three tag single nucleotide polymorphisms (SNPs) of the TIRAP gene and two additional SNPs that have previously showed association with susceptibility to other inflammatory diseases were genotyped by direct sequencing. The differences of allele, genotype and haplotype frequencies were evaluated between three groups.

Results

The minor allele frequencies of both rs595209 and rs8177375 were significantly increased in ALI patients compared with both healthy subjects (odds ratio (OR) = 1.47, 95% confidence interval (CI):1.15-1.88, P = 0.0027 and OR = 1.97, 95% CI: (1.38-2.80), P = 0.0001, respectively) and sepsis alone patients (OR = 1.44, 95% CI: 1.12-1.85, P = 0.0041 and OR = 1.82, 95% CI: 1.28-2.57, P = 0.00079, respectively). Haplotype consisting of these two associated SNPs strengthened the association with ALI susceptibility. The frequency of haplotype AG (rs595209A, rs8177375G) in the ALI samples was significantly higher than that in the healthy control group (OR = 2.13, 95% CI: 1.46-3.09, P = 0.00006) and the sepsis alone group (OR = 2.24, 95% CI: 1.52-3.29, P = 0.00003). Carriers of the haplotype CA (rs595209C, rs8177375A) had a lower risk for ALI compared with healthy control group (OR = 0.69, 95% CI: 0.54-0.88, P = 0.0003) and sepsis alone group (OR = 0.71, 95% CI: 0.55-0.91, P = 0.0006). These associations remained significant after adjustment for covariates in multiple logistic regression analysis and for multiple comparisons.

Conclusions

These results indicated that genetic variants in the TIRAP gene might be associated with susceptibility to sepsis-associated ALI in Han Chinese population. However, the association needs to be replicated in independent studies.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/11/168/prepub

Title: Genetic variants in the TIRAP gene are associated with increased risk of sepsis-associated acute lung injury
Authors: Zhenju Song
Chaoyang Tong
Zhan Sun
Yao Shen
Chenling Yao
Jinjun Jiang
Jun Yin
Lei Gao
Yuanlin Song
Chunxue Bai
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2010
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-11-168

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Genetic variants in the TIRAP gene are associated with increased risk of sepsis-associated acute lung injury

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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