Genetic polymorphism of the type A human natriuretic peptide receptor (NPR-A) gene contributes to the interindividual variability in the BNP system.
OBJECTIVE
To analyse the contribution of recently described genetic polymorphisms in the human natriuretic peptide receptor (NPR-A) to the interindividual variability in the BNP system.


RESULTS
We evaluated NT-proBNP in 402 subjects, including healthy controls (n=93), patients with acute coronary syndrome (n=194) and heart failure (n=115). Three polymorphic sites encoding six common haplotypes of the NPR-A receptor gene, including three haplotypes in the 5' region (CT11, CT10 and CT6) and three haplotypes in the 3' region (3-plus, 4-minus and 4-plus), were studied. The frequency of the identified "4-minus" haplotype was higher in control subjects with high NT-proBNP (>75th percentile) levels as compared to those with low NT-proBNP levels (15.2% vs. 5.7%, p<0.05). In the control subjects, carriers of the "4-plus/4-minus" genotype had about 2-fold higher median NT-proBNP levels than individuals with other genetic variants (142 pg/ml (88-371 pg/ml) vs. 71 pg/ml (35-111 pg/ml, p=0.011). In contrast, in patients with cardiovascular disorders no relation between NT-proBNP and the described polymorphisms was observed.


CONCLUSIONS
The "4-minus" haplotype of the NPR-A receptor gene is associated with high NT-proBNP values and is a genetic determinant of the interindividual variability in the BNP system in healthy individuals but probably not in patients with cardiovascular disorders.
Weber
Michael
M
Kerckhoff Heart Center, Department of Cardiology, Bad Nauheim, Germany. M.Weber@Kerckhoff-Klinik.de
Burian
Maria
M
Dragutinovic
Ivana
I
Moellmann
Helge
H
Nef
Holger
H
Elsaesser
Albrecht
A
Mitrovic
Veselin
V
Hamm
Christian
C
Geisslinger
Gerd
G
D000368:Aged; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006331:Heart Diseases / Q000097:blood* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000502:physiology*; D010446:Peptide Fragments / Q000097:blood*; D011110:Polymorphism, Genetic; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*
D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A