Heritability and genetic linkage of plasma natriuretic peptide levels.
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.


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.
Wang
Thomas J
TJ
Framingham Heart Study, MA 01702-5827, USA.
Larson
Martin G
MG
Levy
Daniel
D
Benjamin
Emelia J
EJ
Corey
Diane
D
Leip
Eric P
EP
Vasan
Ramachandran S
RS
D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12; D002889:Chromosomes, Human, Pair 2; D015331:Cohort Studies; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008297:Male; D008404:Massachusetts; D008875:Middle Aged; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000235:genetics*; D011498:Protein Precursors / Q000097:blood / Q000235:genetics*; D017678:Sex Distribution; D035781:Siblings
C099254:N-terminal proatrial natriuretic peptide; D011498:Protein Precursors; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor