Zeller Tanja, Schurmann Claudia, Schramm Katharina, Müller Christian, Kwon Soonil, Wild Philipp S, Teumer Alexander, Herrington David, Schillert Arne, Iacoviello Licia, Kratzer Adelheid, Jagodzinski Annika, Karakas Mahir, Ding Jingzhong, Neumann Johannes T, Kuulasmaa Kari, Gieger Christian, Kacprowski Tim, Schnabel Renate B, Roden Michael, Wahl Simone, Rotter Jerome I, Ojeda Francisco, Carstensen-Kirberg Maren, Tregouet David-Alexandre, Dörr Marcus, Meitinger Thomas, Lackner Karl J, Wolf Petra, Felix Stephan B, Landmesser Ulf, Costanzo Simona, Ziegler Andreas, Liu Yongmei, Völker Uwe, Palmas Walter, Prokisch Holger, Guo Xiuqing, Herder Christian, Blankenberg Stefan, Homuth Georg
From the General and Interventional Cardiology, University Heart Center Hamburg, Germany (T.Z., C.M., A.J., M.K., J.T.N., R.B.S., F.O., S.B.); DZHK (German Centre for Cardiovascular Research), Germany (T.Z., C.S., C.M., P.S.W., A.T., A.S., A.K., A.J., M.K., J.T.N., T.K., R.B.S., M.D., T.M., K.J.L., S.B.F., U.L., A.Z., U.V., S.B.); Institute of Human Genetics (K.S., T.M., H.P.), Molecular Epidemiology (C.G., S.W.), and Institute of Epidemiology II (C.G., S.W.), Helmholtz Zentrum München, Germany; Institut für Medizinische Biometrie und Statistik, Universitätsklinikum Schleswig-Holstein, Germany (C.M., A.S., A.Z.); Institute for Translational Genomics and Population Sciences, UCLA Medical Center (S.K., J.I.R., X.G.); Preventive Cardiology and Preventive Medicine (P.S.W.), Institute of Clinical Chemistry and Laboratory Medicine (K.J.L.), and Center for Thrombosis and Hemostasis (P.S.W.), University Medical Center of the Johannes Gutenberg-University Mainz, Germany; Institute for Community Medicine (A.T.) and Department of Internal Medicine B (M.D., S.B.F.), University Medicine Greifswald, Germany; Interfaculty Institute for Genetics and Functional Genomics, University Greifswald, Germany (C.S., T.K., U.V., G.H.); Department of Internal Medicine (D.H., J.D.) and Department of Epidemiology and Prevention (Y.L.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli IS, Italy (L.I., S.C.); Department of Cardiology and Pneumology, Charite, Universitätsmedizin Berlin, Germany (A.K., U.L.); National Institute for Health and Welfare, Helsinki, Finland (K.K.); Institute for Clinical Diabetology, German Diabetes Center, Duesseldorf, Germany (M.R., M.C.-K., C.H.); Department of Endocrinology and Diabetology, Medical Faculty Düsseldorf, Germany (M.R.); German Center for Diabetes Research (DZD), Munich, Germany (M.R., S.W., M.C.-K., C.H.); Sorbonne Universités, UPMC, INSERM, UMR_S 1166, ICAN Institute for Cardiometabolism and Nutrition, Paris, France (D.-A.T.); Institute of Human Genetics, Technische Universität München, Germany (T.M., P.W., H.P.); ZIK_FunGene, Universität Greifswald, Germany (U.V., G.H.); and Columbia University Medical Center, New York, NY (W.P.).
Hypertension. 2017 Oct;70(4):743-750. doi: 10.1161/HYPERTENSIONAHA.117.09458. Epub 2017 Aug 7.
Hypertension represents a major cardiovascular risk factor. The pathophysiology of increased blood pressure (BP) is not yet completely understood. Transcriptome profiling offers possibilities to uncover genetics effects on BP. Based on 2 populations including 2549 individuals, a meta-analyses of monocytic transcriptome-wide profiles were performed to identify transcripts associated with BP. Replication was performed in 2 independent studies of whole-blood transcriptome data including 1990 individuals. For identified candidate genes, a direct link between long-term changes in BP and gene expression over time and by treatment with BP-lowering therapy was assessed. The predictive value of protein levels encoded by candidate genes for subsequent cardiovascular disease was investigated. Eight transcripts (, , , , , , and ) were identified jointly accounting for up to 13% (95% confidence interval, 8.7-16.2) of BP variability. Changes in , , , , , , and expression associated with BP changes-among these, gene expression was additionally correlated to measures of cardiac hypertrophy. Assessment of circulating CRIP1 (cystein-rich protein 1) levels as biomarkers showed a strong association with increased risk for incident stroke (hazard ratio, 1.06; 95% confidence interval, 1.03-1.09; =5.0×10). Our comprehensive analysis of global gene expression highlights 8 novel transcripts significantly associated with BP, providing a link between gene expression and BP. Translational approaches further established evidence for the potential use of CRIP1 as emerging disease-related biomarker.
高血压是主要的心血管危险因素。血压升高的病理生理学尚未完全明确。转录组分析为揭示基因对血压的影响提供了可能。基于包含2549名个体的2个群体，对单核细胞转录组全谱进行荟萃分析，以识别与血压相关的转录本。在包含1990名个体的2项全血转录组数据独立研究中进行重复验证。对于鉴定出的候选基因，评估血压长期变化与随时间及通过降压治疗的基因表达之间的直接联系。研究候选基因编码的蛋白质水平对后续心血管疾病的预测价值。共鉴定出8个转录本（、、、、、、和），它们共同解释了高达13%（95%置信区间，8.7 - 16.2）的血压变异性。、、、、、和的表达变化与血压变化相关——其中，基因表达还与心脏肥大指标相关。将循环中的富含半胱氨酸蛋白1（CRIP1）水平作为生物标志物进行评估，结果显示其与中风发病风险增加密切相关（风险比，1.06；95%置信区间，1.03 - 1.09；=5.0×10）。我们对整体基因表达的综合分析突出了8个与血压显著相关的新转录本，建立了基因表达与血压之间的联系。转化研究方法进一步为CRIP1作为新出现的疾病相关生物标志物的潜在用途提供了证据。
