The IL6R variation Asp(358)Ala is a potential modifier of lung function in subjects with asthma.
The IL6R variation Asp(358)Ala is a potential modifier of lung function in subjects with asthma.
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DOI：
10.1016/j.jaci.2012.03.018
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发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
National Heart, Lung, and Blood Institute–sponsored Severe Asthma Research Program (SARP)
中科院分区：
文献类型：
--
作者：
Hawkins GA;Robinson MB;Hastie AT;Li X;Li H;Moore WC;Howard TD;Busse WW;Erzurum SC;Wenzel SE;Peters SP;Meyers DA;Bleecker ER;National Heart, Lung, and Blood Institute–sponsored Severe Asthma Research Program (SARP)
IL6R SNP rs4129267 最近被确定为欧洲血统受试者的哮喘易感位点，但尚未确定哮喘严重程度的特征。 SNP rs4129267 与 IL6R 编码 SNP rs2228145 (Asp358Ala) 连锁不平衡 (r2=1)。这种 IL6R 编码变化增加了 IL6 受体脱落并促进 IL6 信号转导。评估 IL6R SNP rs2228145 与哮喘严重程度表型的关系。 IL6R SNP rs2228145 在来自严重哮喘研究计划 (SARP) 的欧洲血统哮喘受试者中进行了评估。肺功能关联在哮喘遗传学合作研究 (CSGA) 队列中得到了重复。通过 SARP 测量受试者的血清可溶性 IL6 受体 (sIL6R) 水平。使用免疫组织化学定性评估 BAL 细胞和支气管内活检中的 IL6R 蛋白表达。 IL6R SNP rs2228145 的次要 C 等位基因与 SARP 队列 (p=0.005)、CSGA 队列 (0.008) 和组合队列分析 (p=0.003) 中较低的 ppFEV1 相关。观察到与 ppFVC、FEV1/FVC 和 PC20 的其他关联。 rs2228145 C 等位基因 (Ala358) 在严重哮喘表型簇中更为常见。血清 sIL6R 升高与较低的 ppFEV1 (p=0.02) 和较低的 ppFVC (p=0.008) (N=146) 相关。在 BAL 巨噬细胞、气道上皮、血管内皮和气道平滑肌中观察到 IL6R 蛋白表达。 IL6R 编码 SNP rs2228145 (Asp358Ala) 是哮喘肺功能的潜在调节剂，可识别处于更严重哮喘风险的受试者。 IL6 转信号可能在肺部具有致病作用。
The IL6R SNP rs4129267 has recently been identified as an asthma susceptibility locus in subjects of European ancestry but has not been characterized with respect to asthma severity. The SNP rs4129267 is in linkage disequilibrium (r2=1) with the IL6R coding SNP rs2228145 (Asp358Ala). This IL6R coding change increases IL6 receptor shedding and promotes IL6 transsignaling. To evaluate the IL6R SNP rs2228145 with respect to asthma severity phenotypes. The IL6R SNP rs2228145 was evaluated in subjects of European ancestry with asthma from the Severe Asthma Research Program (SARP). Lung function associations were replicated in the Collaborative Study on the Genetics of Asthma (CSGA) cohort. Serum soluble IL6 receptor (sIL6R) levels were measured in subjects from SARP. Immunohistochemistry was used to qualitatively evaluate IL6R protein expression in BAL cells and endobronchial biopsies. The minor C allele of IL6R SNP rs2228145 was associated with lower ppFEV1 in the SARP cohort (p=0.005), the CSGA cohort (0.008), and in combined cohort analysis (p=0.003). Additional associations with ppFVC, FEV1/FVC, and PC20 were observed. The rs2228145 C allele (Ala358) was more frequent in severe asthma phenotypic clusters. Elevated serum sIL6R was associated with lower ppFEV1 (p=0.02) and lower ppFVC (p=0.008) (N=146). IL6R protein expression was observed in BAL macrophages, airway epithelium, vascular endothelium, and airway smooth muscle. The IL6R coding SNP rs2228145 (Asp358Ala) is a potential modifier of lung function in asthma and may identify subjects at risk for more severe asthma. IL6 transsignaling may have a pathogenic role in the lung.
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影响因子：
168.9
作者：
Ferreira, Manuel A. R.;Matheson, Melanie C.;Duffy, David L.;Marks, Guy B.;Hui, Jennie;Le Souef, Peter;Danoy, Patrick;Baltic, Svetlana;Nyholt, Dale R.;Jenkins, Mark;Hayden, Catherine;Willemsen, Gonneke;Ang, Wei;Kuokkanen, Mikko;Beilby, John;Cheah, Faang;de Geus, Eco J. C.;Ramasamy, Adaikalavan;Vedantam, Sailaja;Salomaa, Veikko;Madden, Pamela A.;Heath, Andrew C.;Hopper, John L.;Visscher, Peter M.;Musk, Bill;Leeder, Stephen R.;Jarvelin, Marjo-Riitta;Pennell, Craig;Boomsma, Dorret I.;Hirschhorn, Joel N.;Walters, Haydn;Martin, Nicholas G.;James, Alan;Jones, Graham;Abramson, Michael J.;Robertson, Colin F.;Dharmage, Shyamali C.;Brown, Matthew A.;Montgomery, Grant W.;Thompson, Philip J.
通讯作者：
Thompson, Philip J.
影响因子：
--
作者：
Wilk, Jemma B.;Walter, Robert E.;Laramie, Jason M.;Gottlieb, Daniel J.;O'Connor, George T.
通讯作者：
O'Connor, George T.
DOI：
10.1164/ajrccm.152.3.7663792
发表时间：
1995-09-01
影响因子：
24.7
作者：
通讯作者：
--
影响因子：
5
作者：
Galicia, JC;Tai, H;Yoshie, H
通讯作者：
Yoshie, H
影响因子：
2.1
作者：
Meyers, DA;Wjst, M;Ober, C
通讯作者：
Ober, C