title: Impact of natriuretic peptide clearance receptor (NPR3) gene variants on blood pressure in type 2 diabetes.
abstract: OBJECTIVE
  Hypertension in diabetes is characterized by abnormal sodium homeostasis, suggesting a particular role of natriuretic peptide pathway. Natriuretic peptides can affect blood pressure (BP) through their plasma concentrations, which are dependent on their receptor activities. We thus assessed the association between nine NPR3 gene polymorphisms and BP levels in patients with type 2 diabetes.
  
  
  METHODS
  Nine single nucleotide polymorphisms (SNPs) tagging the haplotype structure of the NPR3 gene were genotyped in the 3,126 French Non-insulin-dependent Diabetes, Hypertension, Microalbuminuria or Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) trial participants. We then used a second population (Diabete de type 2, Nephropathie et Genetique [DIAB2NEPHROGENE]/Survie, Diabete de type 2 et Genetique [SURDIAGENE] study) of 2,452 patients for the purpose of replication. Finally, we separately investigated subjects selected according to their rs 2270915SNP genotypes for their BP response to salt restriction.
  
  
  RESULTS
  In DIABHYCAR patients, three SNPs (rs6889608, rs1173773, and rs2270915) were significantly associated with systolic BP (SBP). The effect of the rs2270915 was replicated in the second step population: AA homozygotes had a lower SBP than G carriers (137.4 ± 19.1 vs. 140.0 ± 20.2 mmHg, P = 0.004). The rs2270915 influenced the response of SBP to salt reduction, with AA homozygous patients showing greater reductions after restriction of salt intake compared with G carriers: -20 mmHg (-43 to -8) vs. -3 (-20 to +7); P = 0.006.
  
  
  CONCLUSIONS
  We found a consistent and significant association between the rs2270915 polymorphism of the NPR3 gene and SBP in diabetic patients. This genetic variation may affect pressure response to changes in dietary sodium.
authors.affiliation: Centre d’investigation clinique, INSERM CIC0802, Centre Hospitalier Universitaire de Poitiers, Poitiers, France. pierre-jean.saulnier@chu-poitiers.fr
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Saulnier
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Halimi
authors.forename: Jeremie
authors.initials: J
authors.lastname: Lebrec
authors.forename: Dured
authors.initials: D
authors.lastname: Dardari
authors.forename: Sulyia
authors.initials: S
authors.lastname: Maimaitiming
authors.forename: Gérard
authors.initials: G
authors.lastname: Guilloteau
authors.forename: Xavier
authors.initials: X
authors.lastname: Prugnard
authors.forename: Richard
authors.initials: R
authors.lastname: Marechaud
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ragot
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
mesh_terms: D001794:Blood Pressure / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*
chemical_list: D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C