Interleukin-6 receptor pathways in abdominal aortic aneurysm.
Interleukin-6 receptor pathways in abdominal aortic aneurysm.
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DOI：
10.1093/eurheartj/ehs354
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发表时间：
2013-12
影响因子：
39.3
通讯作者：
Humphries SE
中科院分区：
文献类型：
--
作者：
Harrison SC;Smith AJ;Jones GT;Swerdlow DI;Rampuri R;Bown MJ;Aneurysm Consortium;Folkersen L;Baas AF;de Borst GJ;Blankensteijn JD;Price JF;van der Graaf Y;McLachlan S;Agu O;Hofman A;Uitterlinden AG;Franco-Cereceda A;Ruigrok YM;van't Hof FN;Powell JT;van Rij AM;Casas JP;Eriksson P;Holmes MV;Asselbergs FW;Hingorani AD;Humphries SE
我们对报告AAA中循环IL-6的研究进行了系统回顾和荟萃分析，并对IL-6 R基因（IL 6 R）中常见的非同义功能变体（Asp 358 Ala）与AAA之间的关联进行了新的研究，随后对体外和体内变体进行了分析。炎症可能在腹主动脉瘤（AAA）的发展中发挥作用。白细胞介素-6（IL-6）通过其受体（IL-6 R）的信号传导是一种可以被开发的途径。我们使用孟德尔随机化方法对此进行了研究。截至2011年10月，我们确定了7项研究（869例病例，851例对照）。Meta分析显示AAA患者IL-6水平高于对照组[标准化均值差（SMD）= 0.46 SD，95%CI = 0.25-0.66，I2 = 70%，P = 1.1 × 10-5随机效应]。对5项研究（4524例病例/15710例对照）的荟萃分析表明，rs7529229（标记非同义变异体Asp 358 Ala，rs 2228145）与AAA的风险较低相关，每个Ala 358等位基因的比值比为0.84，95%CI：0.80-0.89，I2 = 0%，P = 2.7 × 10-11）。在淋巴母细胞系中的体外分析表明，在Ala 358携带者中，响应于IL-6刺激，下游靶标（STAT 3、MYC和ICAM 1）的表达减少。孟德尔随机化方法提供了强有力的证据，表明通过IL-6 R的信号传导可能是AAA的因果途径。抑制IL-6 R的药物可能在AAA管理中发挥作用。
We conducted a systematic review and meta-analysis of studies reporting circulating IL-6 in AAA, and new investigations of the association between a common non-synonymous functional variant (Asp358Ala) in the IL-6R gene (IL6R) and AAA, followed the analysis of the variant both in vitro and in vivo. Inflammation may play a role in the development of abdominal aortic aneurysms (AAA). Interleukin-6 (IL-6) signalling through its receptor (IL-6R) is one pathway that could be exploited pharmacologically. We investigated this using a Mendelian randomization approach. Up to October 2011, we identified seven studies (869 cases, 851 controls). Meta-analysis demonstrated that AAA cases had higher levels of IL-6 than controls [standardized mean difference (SMD) = 0.46 SD, 95% CI = 0.25–0.66, I2 = 70%, P = 1.1 × 10–5 random effects]. Meta-analysis of five studies (4524 cases/15 710 controls) demonstrated that rs7529229 (which tags the non-synonymous variant Asp358Ala, rs2228145) was associated with a lower risk of AAA, per Ala358 allele odds ratio 0.84, 95% CI: 0.80–0.89, I2 = 0%, P = 2.7 × 10–11). In vitro analyses in lymphoblastoid cell lines demonstrated a reduction in the expression of downstream targets (STAT3, MYC and ICAM1) in response to IL-6 stimulation in Ala358 carriers. A Mendelian randomization approach provides robust evidence that signalling via the IL-6R is likely to be a causal pathway in AAA. Drugs that inhibit IL-6R may play a role in AAA management.
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影响因子：
15.8
作者：
Moher D;Liberati A;Tetzlaff J;Altman DG;PRISMA Group
通讯作者：
PRISMA Group
影响因子：
9.8
作者：
Bown, Matthew J.;Jones, Gregory T.;Samani, Nilesh J.
通讯作者：
Samani, Nilesh J.
影响因子：
6
作者：
Lindeman, Jan H. N.;Abdul-Hussien, Hazem;Kleemann, Robert
通讯作者：
Kleemann, Robert
影响因子：
30.8
作者：
Helgadottir, Anna;Thorleifsson, Gudmar;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
3.4
作者：
Kanbe, Katsuaki;Chen, Qian;Hobo, Kaori
通讯作者：
Hobo, Kaori