title: Angiotensin II type 1 receptor 1166C polymorphism is associated with abdominal aortic aneurysm in three independent cohorts.
abstract: OBJECTIVE
  Although polymorphic variations in genes of the RAS system have previously been associated with susceptibility to AAA, such studies have been significantly limited by small sample sizes. This study was undertaken, using the largest case series yet reported, to determine whether common genetic variants of the RAS are associated with either susceptibility or severity of AAA.
  
  
  RESULTS
  The frequencies of 4 common genetic variants of genes related to the renin-angiotensin system were investigated in 3 geographically distinct, but ethnically similar, case-control cohorts, resulting in comparison of 1226 AAA cases with 1723 controls. In all 3 the AGTR1 1166C allele was significantly more common in AAA patients than controls (overall adjusted OR 1.60, 95% CI 1.32 to 1.93, P=1.1x10(-6)). Overall, the ACE ID genotype was associated with AAA (OR 1.33, 95% CI 1.06 to 1.67, P<0.02). The AGT 268T allele appeared to have an epistatic effect on large aneurysm size.
  
  
  CONCLUSIONS
  This study has identified a strong and repeated association between the AGTR1 1166C allele and susceptibility to AAA, and a weaker effect associated with the ACE deletion allele, in 3 geographically distinct, but ethnically similar, case-control cohorts. This study highlights the key role of the RAS in AAA and emphasizes the need for replication and validation of results in suitable independent cohorts.
authors.affiliation: Department of Surgery, University of Otago, New Zealand. greg.jones@otago.ac.nz
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Jones
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Thompson
authors.forename: Frank M
authors.initials: FM
authors.lastname: van Bockxmeer
authors.forename: Hany
authors.initials: H
authors.lastname: Hafez
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Cooper
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Paul E
authors.initials: PE
authors.lastname: Norman
authors.forename: Andre M
authors.initials: AM
authors.lastname: van Rij
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D000808:Angiotensinogen / Q000235:genetics; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D001315:Australia; D001483:Base Sequence; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009520:New Zealand; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000502:physiology; D043782:Receptor, Bradykinin B2 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology; D017384:Sequence Deletion; D006113:United Kingdom
chemical_list: D044140:Receptor, Angiotensin, Type 1; D043782:Receptor, Bradykinin B2; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A