on January 31, 2008
Published online before print January 31, 2008, doi: 10.1161/ATVBAHA.107.155564
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Submitted on September 6, 2007
Accepted on January 16, 2008
Angiotensin II Type 1 Receptor 1166C Polymorphism Is Associated With Abdominal Aortic Aneurysm in Three Independent Cohorts
Gregory T. Jones *;
From the Department of Surgery (G.T.J., A.M.v.R.), University of Otago, New Zealand; the Centre for Cardiovascular Genetics (A.R.T., J.A.C., S.E.H.), British Heart Foundation Laboratories, Royal Free and University College London Medical School, UK; the School of Surgery and Pathology (F.M.v.B., P.E.N.), University of Western Australia, Australia; the Department of Vascular Surgery (H.H.), St Richard’s Hospital, UK; and the Department of Surgery (J.G.), James Cook University, Australia.
* To whom correspondence should be addressed. E-mail: greg.jones{at}otago.ac.nz.
Objectives—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.
Methods and 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 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.
Conclusion—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.
Key words: abdominal aortic aneurysm • angiotensinogen • angiotensin converting enzyme • angiotensin • Bradykinin • genetic association • renin