Human genetics, natriuretic peptides and hypertension

Results We used a candidate gene association study of common variants across the NPPA-NPPB locus to identify genetic variants that influence atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) [1]. The minor alleles of three noncoding SNPs rs5068 (MAF 0.06), rs198358 (MAF 0.19) and rs632793 (MAF 0.38) were associated with higher ANP (+0.42 SD p=8x10-70; +0.20 p=8x10-30; +0.08 p=2x10-10, respectively) and higher BNP (+0.17 SD p=3x10-12, +0.18 p=9x10-25, +0.21 p=2x10-68) in 14,515 individuals of European ancestry. The alleles of rs5068 and rs198358 associated with higher ANP/BNP were associated with lower SBP (p=2x10-6, p=6x10-5, respectively) and lower DBP (p=1x10-6, p=5x10-5) as well as lower odds of HTN (OR 0.85 p=4x10-5, OR 0.90 p=2x10-4) in 29,717 individuals. The association of rs5068 was replicated in the Global BPgen GWAS [2]. Recently, Kato et al reported the association of a common variant downstream of NPR3 encoding the natriuretic peptide clearance receptor [3]. Murine NPR3 knockout is associated with lower BP, consistent with higher levels of circulating natriuretic peptides [4]. The minor allele of a SNP highly correlated to the BP NPR3 SNP has recently been reported to be associated with taller stature in humans [5], consistent with the effect of murine knockout [4] or apparent loss-of-function mutations [6] in NPR3.