Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure

C. Newton-Cheh, M.G. Larson, R.S. Vasan, D. Levy, K. Bloch, A. Surti, C. Guiducci, S. Kathiresan, E.J. Benjamin, J. Struck, N.G. Morgenthaler, A. Bergmann, S. Blankenberg, Frank Kee, P. Nilsson, X. Yin, L. Peltonen, E. Vartiainen, V. Salomaa, J.N. HirschhornO. Melander, T.J. Wang

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Abstract

We examined the association of common variants at the NPPA-NPPB locus with circulating concentrations of the natriuretic peptides, which have blood pressure-lowering properties. We genotyped SNPs at the NPPA-NPPB locus in 14,743 individuals of European ancestry, and identified associations of plasma atrial natriuretic peptide with rs5068 (P = 8 × 10 -70), rs198358 (P = 8 × 10 -30) and rs632793 (P = 2 × 10 -10), and of plasma B-type natriuretic peptide with rs5068 (P = 3 × 10 -12), rs198358 (P = 1 × 10 -25) and rs632793 (P = 2 × 10 -68). In 29,717 individuals, the alleles of rs5068 and rs198358 that showed association with increased circulating natriuretic peptide concentrations were also found to be associated with lower systolic (P = 2 × 10 -6 and 6 × 10 -5, respectively) and diastolic blood pressure (P = 1 × 10 -6 and 5 × 10 -5), as well as reduced odds of hypertension (OR = 0.85, 95% CI = 0.79-0.92, P = 4 × 10 -5; OR = 0.90, 95% CI = 0.85-0.95, P = 2 × 10 -4, respectively). Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension.
Original languageEnglish
Pages (from-to)348-353
Number of pages6
JournalNature Genetics
Volume41
Issue number3
Early online date15 Feb 2009
DOIs
Publication statusPublished - Mar 2009

ASJC Scopus subject areas

  • Genetics

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    Newton-Cheh, C., Larson, M. G., Vasan, R. S., Levy, D., Bloch, K., Surti, A., Guiducci, C., Kathiresan, S., Benjamin, E. J., Struck, J., Morgenthaler, N. G., Bergmann, A., Blankenberg, S., Kee, F., Nilsson, P., Yin, X., Peltonen, L., Vartiainen, E., Salomaa, V., ... Wang, T. J. (2009). Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure. Nature Genetics, 41(3), 348-353. https://doi.org/10.1038/ng.328