title: Polymorphism in the angiotensin II type 1 receptor (AGTR1) is associated with age at diagnosis in pulmonary arterial hypertension.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is a rare, lethal disease associated with single gene disorders, connective tissue disease, exposures to anorexigens, and often, idiopathic etiology. Genes can modify the risk of PAH: (1) monogenic disorders associated with PAH are incompletely penetrant, and (2) not all patients with associated conditions at increased risk for PAH develop the disease. The renin angiotensin aldosterone system (RAAS) provides a set of candidate genes that could modulate pulmonary vascular disease similar to its effects on renal and peripheral vasculature.
  
  
  METHODS
  We studied 247 patients with PAH, comprising 177 with idiopathic PAH (IPAH), 63 with PAH/connective tissue disease (CTD), and 7 with PAH associated with anorexigens. Patients were genotyped for 5 common polymorphisms in angiotensinogen (AGT), angiotensin-converting enzyme (ACE), cardiac chymase A (CMA1), angiotensin II type 1 receptor (AGTR1), and aldosterone synthase (CYP11B2). Genotypes were tested for associations with age at diagnosis, hemodynamic parameters at diagnosis, and/or response to acute pulmonary vasodilator testing at diagnosis.
  
  
  RESULTS
  Associations were demonstrated for AGTR1 and age at diagnosis in IPAH (p = 0.005). Homozygotes for the 1166C allele (n = 13) were associated with an age at diagnosis 26 years later than those with A/A (n = 139) or A/C (n = 90) genotypes. No associations were demonstrated for AGT, ACE, CMA1, or CYP11B2.
  
  
  CONCLUSIONS
  The 1166C polymorphism in AGTR1 appears to be associated with a later age at diagnosis in IPAH, suggesting that this pathway could be involved in the biologic variability that is known to occur in PAH.
authors.affiliation: Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York, USA. wkc15@columbia.edu
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.forename: Liyong
authors.initials: L
authors.lastname: Deng
authors.forename: J Sheila
authors.initials: JS
authors.lastname: Carroll
authors.forename: Nicole
authors.initials: N
authors.lastname: Mallory
authors.forename: Beverly
authors.initials: B
authors.lastname: Diamond
authors.forename: Erika Berman
authors.initials: EB
authors.lastname: Rosenzweig
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.forename: Jane H
authors.initials: JH
authors.lastname: Morse