This Article Full Text Full Text (PDF) All Versions of this Article: 108/1/13    most recent 01.CIR.0000081657.83724.A7v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, T. J. Articles by Vasan, R. S. Search for Related Content PubMed PubMed Citation Articles by Wang, T. J. Articles by Vasan, R. S. Related Collections Cardio-renal physiology/pathophysiology Clinical genetics Epidemiology

(Circulation. 2003;108:13.)
© 2003 American Heart Association, Inc.

Brief Rapid Communication

Heritability and Genetic Linkage of Plasma Natriuretic Peptide Levels

Thomas J. Wang, MD; Martin G. Larson, ScD; Daniel Levy, MD; Emelia J. Benjamin, MD, ScM; Diane Corey, BS; Eric P. Leip, MS; Ramachandran S. Vasan, MD

From the Framingham Heart Study, Framingham, Mass (T.J.W., M.G.L., D.L., E.J.B., D.C., E.P.L., R.S.V.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (T.J.W.); National Heart, Lung, and Blood Institute, Bethesda, Md (D.L.); and Cardiology Section, Boston University School of Medicine, Boston, Mass (D.L., E.J.B., R.S.V.).

Correspondence to Ramachandran Vasan, MD, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702-5827. E-mail vasan{at}fram.nhlbi.nih.gov

Received January 21, 2003; de novo received April 16, 2003; revision received May 16, 2003; accepted May 21, 2003.

Background— Natriuretic peptides play a critical role in the maintenance of salt and water homeostasis and regulation of vascular tone. Thus, interindividual variation in plasma natriuretic peptide levels may contribute to variation in susceptibility to volume overload and hypertension. It is unknown to what extent genetic factors contribute to variation in plasma natriuretic peptide levels.

Methods and Results— We studied 1914 Framingham Study participants (mean age 57 years, 53% women) who underwent routine echocardiography and testing for plasma N-terminal proatrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP). We estimated sex-specific multivariable models and used variance-components methods, implemented in SOLAR (Sequential Oligogenic Linkage Analysis Routines), to estimate heritability. Multipoint linkage analyses were performed using data from a 10-cM-density genome scan. Age, clinical, and echocardiographic variables accounted for 42% and 40% of the variation in log N-ANP and log BNP levels, respectively, in men. Corresponding values in women were 27% and 21%. Multivariable-adjusted heritabilities were 0.44 for log N-ANP and 0.35 for log BNP (P<0.0001). Genome-wide linkage analyses, based on 1142 participants from the 314 largest families, revealed 2 regions of suggestive linkage for log N-ANP and log BNP on chromosomes 2p25 (log-of-odds score 2.40) and 12p13 (log-of-odds score 2.13), respectively.

Conclusions— In this community-based sample, a substantial proportion of the unexplained variation in plasma natriuretic peptide levels was attributable to additive genetic effects. Additional studies using candidate gene approaches may provide insight into the genetic loci that regulate plasma natriuretic peptide levels in humans.

Key Words: natriuretic peptides • genetics • epidemiology • atrial natriuretic factor

This article has been cited by other articles:

				O. Seda, J. Tremblay, D. Gaudet, P.-L. Brunelle, A. Gurau, E. Merlo, L. Pilote, S. N. Orlov, F. Boulva, M. Petrovich, et al. Systematic, Genome-Wide, Sex-Specific Linkage of Cardiovascular Traits in French Canadians Hypertension, April 1, 2008; 51(4): 1156 - 1162. [Abstract] [Full Text] [PDF]

				A. Fijalkowska and A. Torbicki Role of cardiac biomarkers in assessment of RV function and prognosis in chronic pulmonary hypertension Eur. Heart J. Suppl., December 1, 2007; 9(suppl_H): H41 - H47. [Abstract] [Full Text] [PDF]

				E. Ingelsson, M. J. Pencina, G. H. Tofler, E. J. Benjamin, K. J. Lanier, P. F. Jacques, C. S. Fox, J. B. Meigs, D. Levy, M. G. Larson, et al. Multimarker Approach to Evaluate the Incidence of the Metabolic Syndrome and Longitudinal Changes in Metabolic Risk Factors: The Framingham Offspring Study Circulation, August 28, 2007; 116(9): 984 - 992. [Abstract] [Full Text] [PDF]

				W.H. Wilson Tang, G. S. Francis, D. A. Morrow, L. K. Newby, C. P. Cannon, R. L. Jesse, A. B. Storrow, R. H. Christenson, COMMITTEE MEMBERS, R. H. Christenson, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Utilization of Cardiac Biomarker Testing in Heart Failure Circulation, July 31, 2007; 116(5): e99 - e109. [Full Text] [PDF]

				M Gary Nicholls, A Mark Richards, and Christchurch Cardioendocrine Research Group Disease monitoring of patients with chronic heart failure Heart, April 1, 2007; 93(4): 519 - 523. [Full Text] [PDF]

				T. J. Wang, M. G. Larson, M. J. Keyes, D. Levy, E. J. Benjamin, and R. S. Vasan Association of Plasma Natriuretic Peptide Levels With Metabolic Risk Factors in Ambulatory Individuals Circulation, March 20, 2007; 115(11): 1345 - 1353. [Abstract] [Full Text] [PDF]

				A. Nohria and M. M. Givertz B-Type Natriuretic Peptide and the Stressed Heart J. Am. Coll. Cardiol., February 21, 2006; 47(4): 749 - 751. [Full Text] [PDF]

				H. H. Leuchte, M. Holzapfel, R. A. Baumgartner, C. Neurohr, M. Vogeser, and J. Behr Characterization of Brain Natriuretic Peptide in Long-term Follow-up of Pulmonary Arterial Hypertension Chest, October 1, 2005; 128(4): 2368 - 2374. [Abstract] [Full Text] [PDF]

				W.H. W. Tang, J. P. Girod, M. J. Lee, R. C. Starling, J. B. Young, F. Van Lente, and G. S. Francis Plasma B-Type Natriuretic Peptide Levels in Ambulatory Patients With Established Chronic Symptomatic Systolic Heart Failure Circulation, December 16, 2003; 108(24): 2964 - 2966. [Abstract] [Full Text] [PDF]