Allelic variants of natriuretic peptide receptor genes are associated with family history of hypertension and cardiovascular phenotype.
OBJECTIVE
Abnormalities in the natriuretic peptide system could play a key role in the genesis of hypertension. We evaluated the associations between a family history of hypertension, cardiovascular phenotype and allelic variants of Npr1 and Npr3, two candidate genes that codify for natriuretic peptide receptors.


METHODS
We genotyped 45 young normotensive subjects (19 males, 26.8 +/- 3.7 years) with accurately assessed family history of hypertension (FH+) and 52 (26 males, 26.1 +/- 3.1 years) without (FH-) for the known variants of Npr1 and Npr3 genes, and for a novel length difference (3C/4C) polymorphism at position 15129 in the 3'-untranslated region of the Npr1 gene. Blood pressure, echocardiography and plasma brain natriuretic peptide were assessed.


RESULTS
Both the novel Npr1 3C allele (59 versus 33%, P < 0.001) and the 3C/3C genotype (31 versus 8%; P < 0.001) were significantly more frequent in FH+ than in FH-. The inverse distribution of the 4C/4C genotype suggested that a casual association was very unlikely. Moreover, the 3C/3C homozygous had significantly higher systolic blood pressure (121.1 +/- 6.3 versus 115.6 +/- 7.8 mmHg in 4C/4C; P < 0.05) and a longer left ventricular isovolumic relaxation time (67 +/- 10 versus 61 +/- 9 ms; P < 0.05). The Npr3 C(-55) allele variant was also more frequent in FH+ (88 versus 76%, P < 0.05), but was not associated with the cardiovascular phenotype.


CONCLUSIONS
The novel Npr1 gene 3C variant and the Npr3 gene C(-55) allele are associated with hypertensive family history. Moreover, the functional Npr1 3C variant, when homozygous, is also associated with higher systolic blood pressure and prolonged ventricular relaxation.
Pitzalis
Maria Vittoria
MV
Institute of Cardiology, University of Bari, Bari, Italy. mariavittoria.pitzalis@cardio.uniba.it
Sarzani
Riccardo
R
Dessì-Fulgheri
Paolo
P
Iacoviello
Massimo
M
Forleo
Cinzia
C
Lucarelli
Katya
K
Pietrucci
Francesca
F
Salvi
Fabio
F
Sorrentino
Sandro
S
Romito
Roberta
R
Guida
Pietro
P
Rappelli
Alessandro
A
Rizzon
Paolo
P
D000293:Adolescent; D000328:Adult; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*
D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C