Genetic variants in the TIRAP gene are associated with increased risk of sepsis-associated acute lung injury.
Genetic variants in the TIRAP gene are associated with increased risk of sepsis-associated acute lung injury.
复制标题
DOI：
10.1186/1471-2350-11-168
复制
发表时间：
2010-11-30
影响因子：
--
通讯作者：
Bai C
中科院分区：
文献类型：
--
作者：
Song Z;Tong C;Sun Z;Shen Y;Yao C;Jiang J;Yin J;Gao L;Song Y;Bai C
Toll样受体(Toll Like Receptor，TLRs)信号通路，包括TIRAP基因编码的适配蛋白MAL，在急性肺损伤(ALI)的发生发展中起核心作用。最近，TIRAP变异体被描述为与炎症性疾病的易感性有关。本研究的目的是调查TIRAP的遗传变异是否与ALI的发生有关。纳入298例健康汉族人、278例脓毒症相关性ALI和288例单纯脓毒症患者的病例对照研究。TIRAP基因的三个标签单核苷酸多态(SNPs)和另外两个先前已发现与其他炎症性疾病易感性相关的SNPs通过直接测序进行了基因分型。比较三组间等位基因频率、基因型频率和单倍型频率的差异。ALI患者rs595209和rs8177375的等位基因频率均显著高于健康对照组(OR=1.47，95%可信区间：1.15~1.88，P=0.0027和OR=1.97，95%CI：(1.38~2.80)，P=0.0001)和单纯脓毒症患者(OR=1.44，95%CI：1.12~1.85，P=0.0041和OR=1.82，95%CI：1.28~2.57，P=0.05)。P=0.00079)。由这两个相关SNP组成的单倍型加强了与ALI易感性的关联。ALI组AG单倍型频率(rs595209A，rs8177375G)显著高于健康对照组(OR=2.13，95%CI：1.46~3.09，P=0.00006)和单纯脓毒症组(OR=2.24，95%CI：1.52~3.29，P=0.00003)。CA单倍型携带者(rs595209C，rs8177375A)发生ALI的风险低于健康对照组(OR=0.69，95%CI：0.54~0.88，P=0.0003)和单纯脓毒症组(OR=0.71，95%CI：0.55~0.91，P=0.0006)。在对多元Logistic回归分析和多重比较中的协变量进行调整后，这些相关性仍然显著。这些结果提示TIRAP基因的遗传变异可能与中国汉族人群脓毒症相关性ALI的易感性有关。然而，这种关联需要在独立研究中重复。
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. 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. 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. 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.
登录
查看更多内容
影响因子：
64.8
作者：
Horng, T;Barton, GM;Medzhitov, R
通讯作者：
Medzhitov, R
影响因子：
3.2
作者：
Castiblanco, John;Varela, Diana-Cristina;Anaya, Juan-Manuel
通讯作者：
Anaya, Juan-Manuel
DOI：
10.1165/rcmb.2005-0404oc
发表时间：
2006-04-01
影响因子：
6.4
作者：
Gao, L;Grant, A;Garcia, JGN
通讯作者：
Garcia, JGN
DOI：
10.1073/pnas.0811273106
发表时间：
2009-06-23
影响因子：
11.1
作者：
Ferwerda, Bart;Alonso, Santos;Netea, Mihai G.
通讯作者：
Netea, Mihai G.
影响因子：
30.8
作者：
通讯作者：
--