title: Effects of ACE I/D and AT1R-A1166C polymorphisms on blood pressure in a healthy normotensive primary care population: first results of the Hippocates study.
abstract: BACKGROUND
  Several studies have assessed the relationship between the angiotensin-converting enzyme (ACE) I/D or angiotensin II type 1 receptor (AT(1)R)-A C polymorphisms and blood pressure (BP). Since most data have been obtained in selected populations, the present study was performed in a healthy normotensive primary care population.
  
  
  OBJECTIVE
  To investigate the individual effects of the aforementioned polymorphisms and their interaction on BP.
  
  
  METHODS
  This cross-sectional study included 198 healthy subjects. Office BP was measured and polymorphisms were genotyped (polymerase chain reaction). Polymorphism interaction was tested using the following model: systolic blood pressure (SBP) (or diastolic blood pressure, DBP) = b(0)+ b(1)X + b(2)Y + b(3)XY, in which X and Y represent the polymorphisms' risk alleles.
  
  
  RESULTS
  The ACE I/D polymorphism was associated with SBP (P = 0.002) and DBP (P = 0.004); highest pressures tracked with the DD genotype. Furthermore, in multiple linear regression analysis the ACE D allele was associated with SBP (P = 0.005) and DBP (P = 0.001), when adjusted for body mass index (BMI) and age. With respect to the AT(1)R-A C polymorphism, SBP was highest in the CC genotype (P = 0.025). In linear regression analysis the C allele was not associated with SBP. No synergistic effect of ACE D and AT(1)R C alleles on BP was found. Nevertheless, highest DBP tracked with the DDCC combination in comparison with other homozygous allele combinations (P = 0.030).
  
  
  CONCLUSIONS
  This study confirmed an association of ACE I/D and AT(1)R-A C polymorphisms with BP in a healthy normotensive primary care population. Although synergistic effect of both polymorphisms on BP does not seem to be present, an additive effect on DBP is likely.
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), University Hospital, Maastricht University, 6202 AZ Maastricht, The Netherlands.
authors.forename: Léon H
authors.initials: LH
authors.lastname: Henskens
authors.forename: Wilko
authors.initials: W
authors.lastname: Spiering
authors.forename: Henri E
authors.initials: HE
authors.lastname: Stoffers
authors.forename: Frank L
authors.initials: FL
authors.lastname: Soomers
authors.forename: Robert F
authors.initials: RF
authors.lastname: Vlietinck
authors.forename: Peter W
authors.initials: PW
authors.lastname: de Leeuw
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Kroon
mesh_terms: D000225:Adenine; D000368:Aged; D001794:Blood Pressure / Q000235:genetics*; D003430:Cross-Sectional Studies; D003596:Cytosine; D004251:DNA Transposable Elements; D003971:Diastole; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011320:Primary Health Care; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics*; D012016:Reference Values; D013599:Systole
chemical_list: D004251:DNA Transposable Elements; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D003596:Cytosine; D007703:Peptidyl-Dipeptidase A; D000225:Adenine