Lin Honghuang, Joehanes Roby, Pilling Luke C, Dupuis Josée, Lunetta Kathryn L, Ying Sai-Xia, Benjamin Emelia J, Hernandez Dena, Singleton Andrew, Melzer David, Munson Peter J, Levy Daniel, Ferrucci Luigi, Murabito Joanne M
Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.
National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA; Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institute of Health, Bethesda, MD, USA; Population Sciences Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
Genomics. 2014 Dec;104(6 Pt B):490-5. doi: 10.1016/j.ygeno.2014.10.003. Epub 2014 Oct 13.
Circulating interleukin-6 levels increase with advancing age and are a risk factor for various diseases and mortality. The characterization of gene expression profiles associated with interleukin-6 levels might suggest important molecular events underlying its regulation.
We studied the association of transcriptional profiles with interleukin-6 levels in 2422 participants from the Framingham Heart Study Offspring Cohort using Affymetrix Human Exon 1.0 ST Array. We identified 4139 genes that were significantly associated with interleukin-6 levels (FDR<0.05) after adjusting for age, sex and blood cell components. We then replicated 807 genes in the InCHIANTI study with 694 participants. Many of the top genes are involved in inflammation-related pathways or erythrocyte function, including JAK/Stat signaling pathway and interleukin-10 signaling pathway.
We identified and replicated 807 genes that were associated with circulating interleukin-6 levels. Future characterization of interleukin-6 regulation networks may facilitate the identification of additional potential targets for treating inflammation-related diseases.
循环白细胞介素-6水平随年龄增长而升高，是多种疾病和死亡的危险因素。与白细胞介素-6水平相关的基因表达谱特征可能提示其调控背后的重要分子事件。
我们使用Affymetrix Human Exon 1.0 ST Array研究了弗雷明汉心脏研究后代队列中2422名参与者的转录谱与白细胞介素-6水平之间的关联。在调整年龄、性别和血细胞成分后，我们鉴定出4139个与白细胞介素-6水平显著相关的基因（FDR<0.05）。然后我们在有694名参与者的InCHIANTI研究中重复验证了807个基因。许多排名靠前的基因参与炎症相关途径或红细胞功能，包括JAK/Stat信号通路和白细胞介素-10信号通路。
我们鉴定并重复验证了807个与循环白细胞介素-6水平相关的基因。未来对白细胞介素-6调控网络的特征分析可能有助于识别治疗炎症相关疾病的其他潜在靶点。
