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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.

Publication ,  Journal Article
Mitchell, GF; Verwoert, GC; Tarasov, KV; Isaacs, A; Smith, AV; Yasmin, ; Rietzschel, ER; Tanaka, T; Liu, Y; Parsa, A; Najjar, SS; Larson, MG ...
Published in: Circ Cardiovasc Genet
February 1, 2012

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, β=-0.075±0.012 SD/allele, P=2.8×10(-10); replication β=-0.086±0.020 SD/allele, P=1.4×10(-6)). Combined results for rs7152623 from 11 cohorts gave β=-0.076±0.010 SD/allele, P=3.1×10(-15). The association persisted when adjusted for mean arterial pressure (β=-0.060±0.009 SD/allele, P=1.0×10(-11)). Results were consistent in younger (<55 years, 6 cohorts, n=13 914, β=-0.081±0.014 SD/allele, P=2.3×10(-9)) and older (9 cohorts, n=12 026, β=-0.061±0.014 SD/allele, P=9.4×10(-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.

Duke Scholars

Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

February 1, 2012

Volume

5

Issue

1

Start / End Page

81 / 90

Location

United States

Related Subject Headings

  • Young Adult
  • Vascular Stiffness
  • Tumor Suppressor Proteins
  • Risk Factors
  • Repressor Proteins
  • Proportional Hazards Models
  • Phenotype
  • Middle Aged
  • Male
  • Humans
 

Citation

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Mitchell, G. F., Verwoert, G. C., Tarasov, K. V., Isaacs, A., Smith, A. V., Yasmin, ., … Witteman, J. 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. Circ Cardiovasc Genet, 5(1), 81–90. https://doi.org/10.1161/CIRCGENETICS.111.959817
Mitchell, Gary F., Germaine C. Verwoert, Kirill V. Tarasov, Aaron Isaacs, Albert V. Smith, Albert V. Yasmin, Ernst R. Rietzschel, et al. “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.Circ Cardiovasc Genet 5, no. 1 (February 1, 2012): 81–90. https://doi.org/10.1161/CIRCGENETICS.111.959817.
Mitchell GF, Verwoert GC, Tarasov KV, Isaacs A, Smith AV, Yasmin, et al. 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. Circ Cardiovasc Genet. 2012 Feb 1;5(1):81–90.
Mitchell, Gary F., et al. “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.Circ Cardiovasc Genet, vol. 5, no. 1, Feb. 2012, pp. 81–90. Pubmed, doi:10.1161/CIRCGENETICS.111.959817.
Mitchell GF, Verwoert GC, Tarasov KV, Isaacs A, Smith AV, Yasmin, Rietzschel ER, Tanaka T, Liu Y, Parsa A, Najjar SS, O’Shaughnessy KM, Sigurdsson S, De Buyzere ML, Larson MG, Sie MPS, Andrews JS, Post WS, Mattace-Raso FUS, McEniery CM, Eiriksdottir G, Segers P, Vasan RS, van Rijn MJE, Howard TD, McArdle PF, Dehghan A, Jewell ES, Newhouse SJ, Bekaert S, Hamburg NM, Newman AB, Hofman A, Scuteri A, De Bacquer D, Ikram MA, Psaty BM, Fuchsberger C, Olden M, Wain LV, Elliott P, Smith NL, Felix JF, Erdmann J, Vita JA, Sutton-Tyrrell K, Sijbrands EJG, Sanna S, Launer LJ, De Meyer T, Johnson AD, Schut AFC, Herrington DM, Rivadeneira F, Uda M, Wilkinson IB, Aspelund T, Gillebert TC, Van Bortel L, Benjamin EJ, Oostra BA, Ding J, Gibson Q, Uitterlinden AG, Abecasis GR, Cockcroft JR, Gudnason V, De Backer GG, Ferrucci L, Harris TB, Shuldiner AR, van Duijn CM, Levy D, Lakatta EG, Witteman JCM. 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. Circ Cardiovasc Genet. 2012 Feb 1;5(1):81–90.

Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

February 1, 2012

Volume

5

Issue

1

Start / End Page

81 / 90

Location

United States

Related Subject Headings

  • Young Adult
  • Vascular Stiffness
  • Tumor Suppressor Proteins
  • Risk Factors
  • Repressor Proteins
  • Proportional Hazards Models
  • Phenotype
  • Middle Aged
  • Male
  • Humans