Common variants of TLR1 associate with organ dysfunction and sustained pro-inflammatory responses during sepsis.
Common variants of TLR1 associate with organ dysfunction and sustained pro-inflammatory responses during sepsis.
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DOI：
10.1371/journal.pone.0013759
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发表时间：
2010-10-29
期刊：
影响因子：
3.7
通讯作者：
GRECIA and GEN-SEP Groups
中科院分区：
文献类型：
--
作者：
Pino-Yanes M;Corrales A;Casula M;Blanco J;Muriel A;Espinosa E;García-Bello M;Torres A;Ferrer M;Zavala E;Villar J;Flores C;GRECIA and GEN-SEP Groups
Toll样受体（TLR）是宿主病原体识别的关键组分，参与这种反应的基因变异影响对感染的易感性。近年来，TLR 1基因多态性与全血对病原体相关分子的过度炎症反应相关，并与脓毒症相关的多器官功能障碍和急性肺损伤（ALI）相关。我们在一项独立研究中检测了TLR 1基因常见变异与脓毒症并发症的相关性，以及与脓毒症患者血清中四种炎症生物标志物水平的相关性。对一项前瞻性多中心病例研究的样本进行了TLR 1基因7个标记单核苷酸多态性的基因分型，该研究对重症监护病房网络中收治的严重脓毒症患者进行了疾病严重程度随访。在研究开始时、48 h和第7天测定白细胞介素（IL）-1β、IL-6、IL-10和C反应蛋白（CRP）血清水平。等位基因-7202 G和248 Ser以及248 Ser-602 Ile单倍型与严重脓毒症患者的循环功能障碍相关（0.001≤p≤0.022），并与脓毒症发展第一周内血清IL-10水平降低（0.012≤p≤0.047）和CRP水平升高（0.011≤p≤0.036）相关。此外，在对欧洲裔美国人的综合分析中，发现-7202GG基因型与住院死亡率（p = 0.017）和ALI（p = 0.050）相关，表明研究中存在共同的风险效应。 这些结果部分重复和扩展了以前的研究结果，支持TLR 1基因变异是脓毒症严重并发症的决定因素。
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 biomarkers among septic patients. 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)-1β, 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. 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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影响因子：
5.8
作者：
Gonzalez, Juan R.;Armengol, Lluis;Moreno, Victor
通讯作者：
Moreno, Victor
影响因子：
4.4
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通讯作者：
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8.8
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--
DOI：
10.1164/rccm.200603-341oc
发表时间：
2006-06-15
影响因子：
24.7
作者：
Arcaroli, John;Silva, Eliezer;Abraham, Edward
通讯作者：
Abraham, Edward