Association of common variants in NPPA and NPPB with blood pressure does not translate into kidney damage in a general population study.
BACKGROUND
The polymorphisms rs198358, rs5068 and rs632793 in the natriuretic peptide precursor A-B gene region [encoding atrial natriuretic peptides (ANP) and brain natriuretic peptides (BNP)] have been recently associated with ANP and BNP plasma concentrations and blood pressure (BP) in a large cohort study.


METHODS
We observed that GCG, the haplotype based on these polymorphisms and combining the three rare alleles associated with higher natriuretic peptides and lower BP in a recent report, was associated with BNP plasma levels and BP in a French study of 5212 middle-aged participants, Epidemiological Data on Insulin Resistance Syndrome study. With the 9-year follow-up of Epidemiological Data on Insulin Resistance Syndrome study, we were able to analyze the association of incident microalbuminuria (576 patients) and low estimated glomerular filtration rate (<60 ml/min; 246 incident patients) with the tested haplotypes.


RESULTS
No haplotype, including GCG, the one combining the three rare alleles, was associated with incident patients of either microalbuminuria [odds ratio 1.27 (0.91-1.78), P = 0.15] or low estimated glomerular filtration rate [odds ratio 0.88 (0.54-1.46), P = 0.63].


CONCLUSIONS
This was consistent with a lack of effect on clinical renal outcomes found in previous studies and showed that even replicated and biologically plausible genetic association studies based on surrogate markers do not easily translate into clinically meaningful prognosis.
Maimaitiming
Suliya
S
INSERM, U695, Paris, France.
Roussel
Ronan
R
Hadjadj
Samy
S
Fumeron
Frédéric
F
Aubert
Roberte
R
Emery
Nathalie
N
Velho
Gilberto
G
Mohammedi
Kamel
K
Travert
Florence
F
Tichet
Jean
J
Alhenc-Gelas
Francois
F
Balkau
Beverley
B
Marre
Michel
M
D000328:Adult; D001794:Blood Pressure / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D045265:Natriuretic Peptides / Q000235:genetics*; D010641:Phenotype
D045265:Natriuretic Peptides