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

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 x 10(-70)), rs198358 (P = 8 x 10(-30)) and rs632793 (P = 2 x 10(-10)), and of plasma B-type natriuretic peptide with rs5068 (P = 3 x 10(-12)), rs198358 (P = 1 x 10(-25)) and rs632793 (P = 2 x 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 x 10(-6) and 6 x 10(-5), respectively) and diastolic blood pressure (P = 1 x 10(-6) and 5 x 10(-5)), as well as reduced odds of hypertension (OR = 0.85, 95% CI = 0.79-0.92, P = 4 x 10(-5); OR = 0.90, 95% CI = 0.85-0.95, P = 2 x 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.

• Authors: Christopher Newton-Cheh, Martin G Larson, Ramachandran S Vasan, Daniel Levy, Kenneth D Bloch, Aarti Surti, Candace Guiducci, Sekar Kathiresan, Emelia J Benjamin, Joachim Struck, Nils G Morgenthaler, Andreas Bergmann, Stefan Blankenberg, Frank Kee, Peter Nilsson, Xiaoyan Yin, Leena Peltonen, Erkki Vartiainen, Veikko Salomaa, Joel N Hirschhorn, Olle Melander, Thomas J Wang
• Journal: Nature genetics (Nat Genet) Vol. 41 Issue 3 Pg. 348-53 (Mar 2009) ISSN: 1546-1718 [Electronic] United States
• PMID: 19219041 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• NPPA protein, human
• Natriuretic Peptides
• Natriuretic Peptide, Brain
• Atrial Natriuretic Factor

Topics

• Adult
• Aged
• Atrial Natriuretic Factor (genetics)
• Blood Pressure (genetics)
• Case-Control Studies
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Humans
• Hypertension (blood, genetics)
• Linkage Disequilibrium
• Male
• Middle Aged
• Natriuretic Peptide, Brain (genetics)
• Natriuretic Peptides (blood)
• Polymorphism, Single Nucleotide