A novel promoter variant of the natriuretic peptide clearance receptor gene is associated with lower atrial natriuretic peptide and higher blood pressure in obese hypertensives

Riccardo Sarzani, Paolo Dessì-Fulgheri, Fabio Salvi, Massimiliano Serenelli, Diego Spagnolo, Giovanna Cola, Mauro Pupita, Laura Giantomassi, Alessandro Rappelli

Research output: Contribution to journalArticlepeer-review

Abstract

Objective and design. The clearance receptor for natriuretic peptides (NPRC), a candidate gene for essential hypertension, is highly expressed in adipose tissue, where is nutritionally regulated. The objectives of the present study were to sequence the human 5'-flanking regulatory region of NPRC, to identify allelic variants and their frequencies, and to study the genotype/phenotype correlation in hypertensive patients. Methods and results. Using polymerase chain reaction (PCR) and direct automated sequencing, a biallelic (A/C) polymorphism was detected at position -55 in a conserved promoter element named P1. The novel C(-55) variant makes the promoter sequence identical to the mouse gene and introduces a second Hgal site in the amplified DNA, allowing the genotyping of a large number of subjects. In a random sample of 232 white Caucasians the C(-55) allele was more commonly found (81.7% of all alleles) with 155 CC (66.8%), 69 AC (29.7%) and only eight AA (3.5%) genotypes. Atrial natriuretic peptide (ANP) levels were determined in 84 patients with essential hypertension. In the presence of obesity (body mass index (BMI) ≥ 30 kg/m2) the homozygous CC hypertensives (n = 21) had significantly lower plasma ANP (33.6 ± 11.1 pg/ml) compared with the AC patients (n = 11; 46.8 ± 15.9 pg/ml; P = 0.01), whereas systolic blood pressure (SBP) and mean blood pressure (MBP) had the opposite association (SBP 163.9 ± 18.7 versus 150.9 ± 12.9 and MBP 123.3 ± 12 versus 114.5 ± 5.9 mmHg; P <0.05). The difference in ANP levels were also present when overweight patients (BMI ≥ 27 kg/m2) were considered. Conclusion. A common 'ancestral' C(-55) variant of the NPRC P1 promoter is associated with lower ANP levels and higher SBP and MBP in obese hypertensives. The C(-55) variant, in the presence of increased adiposity, might reduce plasma ANP through increased NPRC-mediated ANP clearance, contributing to higher blood pressure.

Original languageEnglish
Pages (from-to)1301-1305
Number of pages5
JournalJournal of Hypertension
Volume17
Issue number9
DOIs
Publication statusPublished - 1999

Keywords

  • Alleles
  • Atrial natriuretic peptide
  • Clearance receptor
  • Hypertension
  • Obesity
  • Promoter

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine

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