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Published on: April 19, 2013
Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure
Tanja Zeller1, Claudia Schurmann2, Katharina Schramm2
1From 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.). t.zeller@uke.de.
Eight novel transcripts were identified, explaining up to 13% of blood pressure variability. Gene expression changes correlate with blood pressure fluctuations, and CRIP1 shows potential as a biomarker for stroke risk.
Area of Science:
- Genomics
- Cardiovascular Medicine
- Biomarker Discovery
Background:
- Hypertension is a primary cardiovascular risk factor with incompletely understood pathophysiology.
- Transcriptome profiling offers a method to investigate genetic influences on blood pressure (BP).
Purpose of the Study:
- To identify novel transcripts associated with blood pressure using meta-analysis of transcriptome-wide data.
- To evaluate the relationship between gene expression, BP changes, and cardiovascular disease risk.
Main Methods:
- Meta-analysis of monocytic transcriptome-wide profiles from 2549 individuals.
- Replication in 2 independent whole-blood transcriptome studies (1990 individuals).
- Assessment of gene expression changes over time and in response to BP-lowering therapy.
- Investigation of protein levels as predictors of cardiovascular disease.
Main Results:
- Eight transcripts (CRIP1, MYADM, TIPARP, TSC22D3, CEBPA, F12, LMNA, TPPP3) were identified, explaining up to 13% of BP variability.
- Expression of CRIP1, MYADM, TIPARP, LMNA, TSC22D3, CEBPA, and TPPP3 correlated with BP changes.
- CRIP1 gene expression linked to cardiac hypertrophy.
- Circulating CRIP1 levels associated with increased stroke risk (HR 1.06, 95% CI 1.03-1.09).
Conclusions:
- Identified 8 novel transcripts significantly associated with blood pressure.
- Demonstrated a link between gene expression and blood pressure regulation.
- Established potential of CRIP1 as a disease biomarker for cardiovascular risk, particularly stroke.
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