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

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BMC Medical Genetics

, 11:168

Genetic epidemiology and genetic associations


BackgroundToll 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.

MethodsA 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.

ResultsThe 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.

ConclusionsThese 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.

AbbreviationsTLRstoll like receptors

ALIacute lung injury

SNPsingle nucleotide polymorphism

ORodds ratio

CIconfidence interval

ARDSacute respiratory distress syndrome

ICUintensive care unit

TIRAPTIR domain-containing adaptor protein

NF-κBnuclear factor-κB


AECCAmerican-European consensus conference statements

APACHEacute physiology and chronic health evaluation

MAFminor allele frequency

BMIbody mass index

LDlinkage disequilibrium

UTRuntranslated region.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-11-168 contains supplementary material, which is available to authorized users.

Zhenju Song, Chaoyang Tong, Zhan Sun contributed equally to this work.

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Author: Zhenju Song - Chaoyang Tong - Zhan Sun - Yao Shen - Chenling Yao - Jinjun Jiang - Jun Yin - Lei Gao - Yuanlin Song - Chun


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