Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure.
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.
Newton-Cheh
Christopher
C
Center for Human Genetic Research, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA. cnewtoncheh@chgr.mgh.harvard.edu
Larson
Martin G
MG
Vasan
Ramachandran S
RS
Levy
Daniel
D
Bloch
Kenneth D
KD
Surti
Aarti
A
Guiducci
Candace
C
Kathiresan
Sekar
S
Benjamin
Emelia J
EJ
Struck
Joachim
J
Morgenthaler
Nils G
NG
Bergmann
Andreas
A
Blankenberg
Stefan
S
Kee
Frank
F
Nilsson
Peter
P
Yin
Xiaoyan
X
Peltonen
Leena
L
Vartiainen
Erkki
E
Salomaa
Veikko
V
Hirschhorn
Joel N
JN
Melander
Olle
O
Wang
Thomas J
TJ
D000328:Adult; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000235:genetics*; D045265:Natriuretic Peptides / Q000097:blood*; D020641:Polymorphism, Single Nucleotide
C472955:NPPA protein, human; D045265:Natriuretic Peptides; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor