title: Angiotensinogen promoter haplotypes are associated with blood pressure in untreated hypertensives.
abstract: BACKGROUND
  The polymorphic angiotensinogen (AGT) gene is one of the most promising candidates for blood pressure (BP) regulation and essential hypertension.
  
  
  OBJECTIVE
  To investigate whether AGT haplotype analysis adds significant information compared to single polymorphism analysis with respect to different BP phenotypes in an untreated hypertensive sample.
  
  
  METHODS
  Two hundred and twelve untreated hypertensive subjects of Caucasian origin were genotyped for the AGT polymorphisms C-532T, A-20C, C-18T, and G-6A.
  
  
  RESULTS
  In single variant analyses, untreated hypertensives, carrying the AGT -532T or -6A alleles had significantly higher systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as ambulatory BP values compared to respective non-carriers. In haplotype-based analyses, combining all four AGT promoter variants, we demonstrate that AGT haplotypes containing different allele combinations at positions -532 and -6 were significantly associated with different BP values: (1) -532T and -6A with higher, (2) -532C and -6G with lower, (3) -532C and -6A with intermediate BP values. Since the result for the -532C/-20A/-18C/-6G haplotype was due to differences between non-carriers and carriers of this haplotype on both chromosomes, a recessive inheritance model for BP effects could be assumed.
  
  
  CONCLUSIONS
  Our results designate the C-532T and G-6A as the best candidates for functional studies on the AGT gene. Haplotype-based analyses should greatly aid in the dissection of the genetic basis of complex traits, such as BP regulation and hypertension.
authors.affiliation: Institute for Arteriosclerosis Research, Department of Molecular Genetics of Cardiovascular Disease, University of Muenster, Germany.
authors.forename: Stefan-Martin
authors.initials: SM
authors.lastname: Brand-Herrmann
authors.forename: Karla
authors.initials: K
authors.lastname: Köpke
authors.forename: Florian
authors.initials: F
authors.lastname: Reichenberger
authors.forename: Klaus
authors.initials: K
authors.lastname: Schmidt-Petersen
authors.forename: Thomas
authors.initials: T
authors.lastname: Reineke
authors.forename: Martin
authors.initials: M
authors.lastname: Paul
authors.forename: Walter
authors.initials: W
authors.lastname: Zidek
authors.forename: Eva
authors.initials: E
authors.lastname: Brand
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D015810:Linkage Disequilibrium; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D044465:White People / Q000235:genetics
chemical_list: D000808:Angiotensinogen