title: Confirmation that the renin gene distal enhancer polymorphism REN-5312C/T is associated with increased blood pressure.
abstract: BACKGROUND
  Studies of knockout and transgenic mice have demonstrated key roles for genes encoding components of the renin angiotensin system in blood pressure regulation. However, whether polymorphisms in these genes contribute to the cause of essential hypertension in humans is still a matter of debate.
  
  
  RESULTS
  We performed an experiment with dense tagging single-nucleotide polymorphism coverage of 4 genes encoding proteins that control the overall activity of the cascade, namely renin, angiotensinogen, angiotensin-converting enzyme, and angiotensin-converting enzyme 2, in 2 Irish populations. Both clinic and 24-hour ambulatory blood pressure measurements were available from population I (n=387), whereas just clinic blood pressure was measured in population II (n=1024). Of the 23 polymorphisms genotyped, only a single renin gene polymorphism, REN-5312C/T, showed consistent statistically significant associations with elevated diastolic pressures. Carriage of one REN-5312T allele was associated with the following age- and sex-adjusted increments in diastolic pressures (mean [95% CI]): population I, clinic, 1.5 mm Hg (0.3 to 2.8); daytime, 1.4 mm Hg (0.4 to 2.4); night-time, 1.3 mm Hg (0.4 to 2.3), and population II, clinic, 1.1 mm Hg (0.1 to 2.1). Haplotypic analyses and multivariate stepwise regression analyses were in concordance with individual single-nucleotide polymorphism analyses.
  
  
  CONCLUSIONS
  The REN-5312T allele had been shown previously to result in increased in vitro expression of the renin gene. We have now shown, in 2 independent populations, that carriage of a REN-5312T allele is associated with elevated diastolic blood pressure. These data provide evidence that renin is an important susceptibility gene for arterial hypertension in whites.
authors.affiliation: Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Belfield, Dublin, Ireland. cvangjeli@rcsi.ie
authors.forename: Ciara
authors.initials: C
authors.lastname: Vangjeli
authors.forename: Niamh
authors.initials: N
authors.lastname: Clarke
authors.forename: Ursula
authors.initials: U
authors.lastname: Quinn
authors.forename: Patrick
authors.initials: P
authors.lastname: Dicker
authors.forename: Orna
authors.initials: O
authors.lastname: Tighe
authors.forename: Clara
authors.initials: C
authors.lastname: Ho
authors.forename: Eoin
authors.initials: E
authors.lastname: O'Brien
authors.forename: Alice V
authors.initials: AV
authors.lastname: Stanton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000085962:Angiotensin-Converting Enzyme 2; D000808:Angiotensinogen / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007494:Ireland; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012083:Renin / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; D012083:Renin