on December 14, 2006
Published online before print December 14, 2006, doi: 10.1161/01.ATV.0000255560.49503.4e
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Submitted on September 13, 2006
Accepted on December 1, 2006
Association Between Osteopontin and Human Abdominal Aortic Aneurysm
Jonathan Golledge *;
From the Vascular Biology Unit (J.G., J.M., P.C., C.M.), School of Medicine, James Cook University, Townsville; the Laboratory for Genetic Epidemiology (N.S., L.J.P.), Western Australian Institute for Medical Research, Perth; the Department of Vascular Surgery (A.E.D.), Monash University, Box Hill Hospital, Box Hill, Melbourne; and the School of Surgery and Pathology (L.S., P.N.), University of Western Australia, Fremantle Hospital, Fremantle, Australia.
* To whom correspondence should be addressed. E-mail: Jonathan.Golledge{at}jcu.edu.au.
Objectives--In vitro and animal studies have implicated osteopontin (OPN) in the pathogenesis of aortic aneurysm. The relationship between serum concentration of OPN and variants of the OPN gene with human abdominal aortic aneurysm (AAA) was investigated.
Methods and Results--OPN genotypes were examined in 4227 subjects in which aortic diameter and clinical risk factors were measured. Serum OPN was measured by ELISA in two cohorts of 665 subjects. The concentration of serum OPN was independently associated with the presence of AAA. Odds ratios (and 95% confidence intervals) for upper compared with lower OPN tertiles in predicting presence of AAA were 2.23 (1.29 to 3.85, P=0.004) for the population cohort and 4.08 (1.67 to 10.00, P=0.002) for the referral cohort after adjusting for other risk factors. In 198 patients with complete follow-up of aortic diameter at 3 years, initial serum OPN predicted AAA growth after adjustment for other risk factors (standardized coefficient 0.24, P=0.001). The concentration of OPN in the aortic wall was greater in patients with small AAAs (30 to 50 mm) than those with aortic occlusive disease alone. There was no association between five single nucleotide polymorphisms or haplotypes of the OPN gene and aortic diameter or AAA expansion.
Conclusions--Serum and tissue concentrations of OPN are associated with human AAA. We found no relationship between variation of the OPN gene and AAA. OPN may be a useful biomarker for AAA presence and growth.
Key words: abdominal aortic aneurysm • genetic polymorphisms • osteopontin
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