title: Allelic variants of natriuretic peptide receptor genes are associated with family history of hypertension and cardiovascular phenotype.
abstract: 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.
authors.affiliation: Institute of Cardiology, University of Bari, Bari, Italy. mariavittoria.pitzalis@cardio.uniba.it
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Pitzalis
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sarzani
authors.forename: Paolo
authors.initials: P
authors.lastname: Dessì-Fulgheri
authors.forename: Massimo
authors.initials: M
authors.lastname: Iacoviello
authors.forename: Cinzia
authors.initials: C
authors.lastname: Forleo
authors.forename: Katya
authors.initials: K
authors.lastname: Lucarelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Pietrucci
authors.forename: Fabio
authors.initials: F
authors.lastname: Salvi
authors.forename: Sandro
authors.initials: S
authors.lastname: Sorrentino
authors.forename: Roberta
authors.initials: R
authors.lastname: Romito
authors.forename: Pietro
authors.initials: P
authors.lastname: Guida
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rappelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Rizzon
mesh_terms: 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*
chemical_list: D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C