The association of interleukin 6 haplotype clades with mortality in critically ill adults
The association of interleukin 6 haplotype clades with mortality in critically ill adults
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DOI：
10.1001/archinte.165.1.75
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发表时间：
2005-01-10
影响因子：
--
通讯作者：
Russell, JA
中科院分区：
文献类型：
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作者：
Sutherland, AM;Walley, KR;Russell, JA
背景：白细胞介素6 （IL-6）是全身性炎症反应综合征（SIRS）中关键的促炎细胞因子。IL-6基因的G- >c多态性反位-174与许多炎症性疾病的不良结果相关，尽管其与败血症的相关性尚不清楚。我们检验了IL-6的特定单倍型分支可能与SIRS结果相关的假设。方法：我们研究了228例危重白人患者，他们至少符合4项SIRS标准中的2项。入院后28天收集临床资料。IL-6的单倍型使用PHASE（用于单倍型重建和从群体数据中估计重组率的软件）从公开的数据中推断，分支结构使用分子进化遗传分析（MEGA2）软件确定。然后，选择一组最小的“单倍型标签”单核苷酸多态性（-174G/C， 1753 C/G和2954G/C）来定义IL-6基因的所有4个主要单倍型分支，进行进一步的基因分型。结果：在单倍型分支-174C/1753C/ 2954G （C/C/G）、G/G/G或G/C/C中携带2个单倍型拷贝的患者与携带1个或没有这些单倍型拷贝的患者相比，28天死亡率更高（40.0% vs 26.0%； P= 0.02）。这些患者的生存时间也更短，没有多系统器官功能障碍(P
Background: Interleukin 6 (IL-6) is a key proinflammatory cytokine in the systemic inflammatory response syndrome (SIRS). A G-->C polymorphism atposition -174 of the IL-6 gene is associated with an adverse outcome in a number of inflammatory diseases, although its association with sepsis as an outcome remains unclear. We tested the hypothesis that specific haplotype clades of IL-6 may be associated with an outcome of SIRS.Methods: We studied a cohort of 228 critically ill white patients who met at least 2 of 4 SIRS criteria. Clinical data were collected over 28 days after hospital admission. Haplotypes of IL-6 were inferred from publicly available data using PHASE (software for haplotype reconstruction and recombination rate estimation from population data), and cladistic structure was determined using Molecular Evolutionary Genetic Analyses (MEGA2) software. Then, a minimum set of "haplotype tag" single nucleotide polymorphisms (-174G/C, 1753 C/G, and 2954G/C) that defined all 4 major haplotype clades of the IL-6 gene was chosen for further genotyping.Results: Patients who had 2 copies of haplotypes from within the haplotype clades -174C/1753C/ 2954G (C/C/G), G/G/G, or G/C/C had a greater 28-day mortality compared with patients who carried 1 or no copies of these haplotypes (40.0% vs 26.0%; P=.02). These patients also had fewer days alive and free of multiple system organ dysfunction (P