title: 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.
abstract: OBJECTIVE
  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.
  
  
  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) > or = 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 > or = 27 kg/m2) were considered.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Clinical Medicine, University of Ancona, Italy. sarzani@popcsi.unian.it
authors.forename: R
authors.initials: R
authors.lastname: Sarzani
authors.forename: P
authors.initials: P
authors.lastname: Dessì-Fulgheri
authors.forename: F
authors.initials: F
authors.lastname: Salvi
authors.forename: M
authors.initials: M
authors.lastname: Serenelli
authors.forename: D
authors.initials: D
authors.lastname: Spagnolo
authors.forename: G
authors.initials: G
authors.lastname: Cola
authors.forename: M
authors.initials: M
authors.lastname: Pupita
authors.forename: L
authors.initials: L
authors.lastname: Giantomassi
authors.forename: A
authors.initials: A
authors.lastname: Rappelli
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood*; D001794:Blood Pressure / Q000235:genetics*; D015992:Body Mass Index; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
chemical_list: D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C