Mitchell, Gary F. and Verwoert, Germaine C. and Tarasov, Kirill V. and Isaacs, Aaron and Smith, Albert V. and Yasmin, and Rietzschel, Ernst R. and Tanaka, Toshiko and Liu, Yongmei and Parsa, Afshin and Najjar, Samer S. and O'Shaughnessy, Kevin M. and Sigurdsson, Sigurdur and De Buyzere, Marc L. and Larson, Martin G. and Sie, Mark P. S. and Andrews, Jeanette S. and Post, Wendy S. and Mattace-Raso, Francesco U. S. and McEniery, Carmel M. and Eiriksdottir, Gudny and Segers, Patrick and Vasan, Ramachandran S. and van Rijn, Marie Josee E. and Howard, Timothy D. and McArdle, Patrick F. and Dehghan, Abbas and Jewell, Elizabeth S. and Newhouse, Stephen J. and Bekaert, Sofie and Hamburg, Naomi M. and Newman, Anne B. and Hofman, Albert and Scuteri, Angelo and De Bacquer, Dirk and Ikram, Mohammad Arfan and Psaty, Bruce M. and Fuchsberger, Christian and Olden, Matthias and Wain, Louise V. and Elliott, Paul and Smith, Nicholas L. and Felix, Janine F. and Erdmann, Jeanette and Vita, Joseph A. and Sutton-Tyrrell, Kim and Sijbrands, Eric J. G. and Sanna, Serena and Launer, Lenore J. and De Meyer, Tim and Johnson, Andrew D. and Schut, Anna F. C. and Herrington, David M. and Rivadeneira, Fernando and Uda, Manuela and Wilkinson, Ian B. and Aspelund, Thor and Gillebert, Thierry C. and Van Bortel, Luc and Benjamin, Emelia J. and Oostra, Ben A. and Ding, Jingzhong and Gibson, Quince and Uitterlinden, Andre G. and Abecasis, Goncalo R. and Cockcroft, John R. and Gudnason, Vilmundur and De Backer, Guy G. and Ferrucci, Luigi and Harris, Tamara B. and Shuldiner, Alan R. and van Duijn, Cornelia M. and Levy, Daniel and Lakatta, Edward G. and Witteman, Jacqueline C. M. (2012) Common Genetic Variation in the 3 '-BCL11B Gene Desert Is Associated With Carotid-Femoral Pulse Wave Velocity and Excess Cardiovascular Disease Risk The AortaGen Consortium. CIRCULATION-CARDIOVASCULAR GENETICS, 5 (1). pp. 81-90. ISSN 1942-325X, 1942-3268
Full text not available from this repository. (Request a copy)Abstract
Background-Carotid-femoral pulse wave velocity (CFPWV) is a heritable measure of aortic stiffness that is strongly associated with increased risk for major cardiovascular disease events. Methods and Results-We conducted a meta-analysis of genome-wide association data in 9 community-based European ancestry cohorts consisting of 20 634 participants. Results were replicated in 2 additional European ancestry cohorts involving 5306 participants. Based on a preliminary analysis of 6 cohorts, we identified a locus on chromosome 14 in the 3'-BCL11B gene desert that is associated with CFPWV (rs7152623, minor allele frequency=0.42, beta=-0.075 +/- 0.012 SD/allele, P=2.8x10(-10); replication beta=-0.086 +/- 0.020 SD/allele, P=1.4x10(-6)). Combined results for rs7152623 from 11 cohorts gave beta=-0.076 +/- 0.010 SD/allele, P=3.1x10(-15). The association persisted when adjusted for mean arterial pressure (beta=-0.060 +/- 0.009 SD/allele, P=1.0x10(-11)). Results were consistent in younger (<55 years, 6 cohorts, n=13 914, beta =-0.081 +/- 0.014 SD/allele, P=2.3x10(-9)) and older (9 cohorts, n=12 026, beta=-0.061 +/- 0.014 SD/allele, P=-9.4x10(-6)) participants. In separate meta-analyses, the locus was associated with increased risk for coronary artery disease (hazard ratio=1.05; confidence interval=1.02-1.08; P=0.0013) and heart failure (hazard ratio=1.10, CI=1.03-1.16, P=0.004). Conclusions-Common genetic variation in a locus in the BCL11B gene desert that is thought to harbor 1 or more gene enhancers is associated with higher CFPWV and increased risk for cardiovascular disease. Elucidation of the role this novel locus plays in aortic stiffness may facilitate development of therapeutic interventions that limit aortic stiffening and related cardiovascular disease events. (Circ Cardiovasc Genet. 2012;5:81-90.)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; ARTERIAL STIFFNESS; AORTIC STIFFNESS; T-CELL; INDEPENDENT PREDICTOR; BLOOD-PRESSURE; RECEPTOR; PROMOTER; VARIANTS; GENOTYPE; aorta; arterial stiffness; pulse wave velocity; genetics; cardiovascular disease |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 May 2020 04:38 |
| Last Modified: | 20 May 2020 04:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19247 |
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