Inter-ethnic differences in lymphocyte sensitivity to glucocorticoids reflect variation in transcriptional response.
Inter-ethnic differences in lymphocyte sensitivity to glucocorticoids reflect variation in transcriptional response.
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DOI：
10.1038/tpj.2011.55
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Di Rienzo A
中科院分区：
文献类型：
--
作者：
Maranville JC;Baxter SS;Torres JM;Di Rienzo A
糖皮质激素（Glucocorticoid，GC）是一种广泛应用于药物干预的甾体激素，主要通过调节基因表达水平发挥作用。很大一部分患者（约30%），特别是非洲裔患者，对治疗反应较弱。为了探究不同转录反应对种族间差异的贡献，我们测量了来自非洲裔美国人和欧洲裔美国人健康供体的外周血单核细胞（PBMC）中体外淋巴细胞GC敏感性（LGS）和全转录组对GC的反应。我们发现处理8小时后的转录反应与群体内和群体间LGS的变化显著相关。我们发现，NFKB1，一个以前发现的预测人群中LGS的基因，平均在欧洲裔美国人中下调更强烈。然而，NFKB 1不能完全解释群体差异，我们发现另外177个基因在平均log2倍数变化（FDR<0.05）上具有群体差异，其中大多数在非洲裔美国人中也显示出较弱的转录反应。这些结果表明，GC敏感性的种族间差异反映了许多基因转录反应的变化，包括具有较大影响的调节因子（例如NFKB 1）和许多其他具有较小影响的基因。
Glucocorticoids (GCs) are steroid hormones widely used as pharmaceutical interventions, which act mainly by regulating gene expression levels. A large fraction of patients (~30%), especially those of African descent, show a weak response to treatment. To interrogate the contribution of variable transcriptional response to inter-ethnic differences, we measured in vitro lymphocyte GC sensitivity (LGS) and transcriptome-wide response to GCs in peripheral blood mononuclear cells (PBMCs) from African-American and European-American healthy donors. We found that transcriptional response after 8hrs treatment was significantly correlated with variation in LGS within and between populations. We found that NFKB1, a gene previously found to predict LGS within populations, was more strongly down-regulated in European-Americans on average. NFKB1 could not completely explain population differences, however, and we found an additional 177 genes with population differences in the average log2 fold change (FDR<0.05), most of which also showed a weaker transcriptional response in African-Americans. These results suggest that inter-ethnic differences in GC sensitivity reflect variation in transcriptional response at many genes, including regulators with large effects (e.g. NFKB1) and numerous other genes with smaller effects.
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影响因子：
9.6
作者：
Federico, MJ;Covar, RA;Spahn, JD
通讯作者：
Spahn, JD
T细胞和B细胞静止的损失是在GIMAP5缺陷型小鼠中微生物菌群依赖的浪费疾病和肠炎的发作之前。
DOI：
10.4049/jimmunol.0903164
发表时间：
2010-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Barnes MJ;Aksoylar H;Krebs P;Bourdeau T;Arnold CN;Xia Y;Khovananth K;Engel I;Sovath S;Lampe K;Laws E;Saunders A;Butcher GW;Kronenberg M;Steinbrecher K;Hildeman D;Grimes HL;Beutler B;Hoebe K
通讯作者：
Hoebe K
影响因子：
6.7
作者：
Drazen, JM;Silverman, EK;Lee, TH
通讯作者：
Lee, TH
影响因子：
14.2
作者：
ALVAREZ, J;SURS, W;SZEFLER, SJ
通讯作者：
SZEFLER, SJ
影响因子：
3.9
作者：
Bray, PJ;Cotton, RGH
通讯作者：
Cotton, RGH