Allelic variants of natriuretic peptide receptor genes are associated with family history of hypertension and cardiovascular phenotype

Maria Vittoria Pitzalis, Riccardo Sarzani, Paolo Dessi-Fulgheri, Massimo Iacoviello, Cinzia Forleo, Katya Lucarelli, Francesca Pietrucci, Fabio Salvi, Sandro Sorrentino, Roberta Romito, Pietro Guida, Alessandro Rappelli, Paolo Rizzon

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1491-1496
Number of pages6
JournalJournal of Hypertension
Volume21
Issue number8
DOIs
Publication statusPublished - Aug 1 2003

Keywords

  • Genetics
  • Hypertension
  • Natriuretic peptides
  • Receptors
  • Risk factors

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

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