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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2120.)
© 2007 American Heart Association, Inc.

Vascular Biology

Association of OAZ1 Gene Polymorphisms With Subclinical and Clinical Vascular Events

Julie Dumont; Mahmoud Zureik; Christophe Bauters; Marie-Catherine Grupposo; Dominique Cottel; Michèle Montaye; Martial Hamon; Pierre Ducimetière; Philippe Amouyel; Thierry Brousseau

From Inserm, U744 (J.D., M.Z., C.B., M.C.G., D.C., M.M., P.A., T.B), Lille; Institut Pasteur de Lille (J.D., M.Z., C.B., M.C.G., D.C., M.M., P.A., T.B.), Lille; Université de Lille 2 (J.D., M.Z., C.B., M.C.G., D.C., M.M., P.A., T.B.), UMR-S744, Lille; Inserm, U780 (P.D.), Villejuif; Paris-Sud (P.D.), UMR-S780; CHRU de Lille (C.B.), Lille; CHU de Caen (M.H.), Caen, France.

Correspondence to Philippe Amouyel, MD, PhD, Inserm, U744, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, F-59019 Lille cedex, France. E-mail Philippe.Amouyel{at}pasteur-lille.fr

Objective— Proliferation and migration of vascular smooth muscle cells (VSMCs) are striking features shared by vascular ageing, atherosclerosis, and in-stent restenosis. VSMC biology depends in part on polyamines whose metabolism is closely regulated by ornithine decarboxylase antizyme 1 (OAZ1). Therefore, we sought for association between OAZ1 gene polymorphisms and various outcomes involving VSMC proliferation.

Methods and Results— Systematic screening of the OAZ1 gene enabled to detect 21 variants. The impact of 4 selected tag polymorphisms (+849C/T, +851G/T, +1804G/A, and +2222A/G) was evaluated in 3 independent association studies. In a sample of 205 patients, the +2222G allele was associated with an increased risk of 6-month coronary in-stent restenosis (OR [95%CI]=2.1 [1.2 to 3.6]; P=0.0071). In a sample of 1001 subjects participating to the EVA study, the +2222G allele was longitudinally associated with a 4-year increase in common carotid intima-media thickness (P=0.047). In a case-control study (466 cases versus 466 controls), the risk of coronary heart disease associated with the +2222G allele was 1.3 (95%CI=[1.1 to 1.6]; P=0.026). No other significant association was consistently detected.

Conclusions— We identified the OAZ1+2222A/G polymorphism as a potential genetic marker of vascular events. Our findings strengthen the hypothesis that the polyamine metabolism plays a role in vascular diseases.

The impact of OAZ1 gene polymorphisms on coronary in-stent restenosis risk, common carotid intima-media thickness, and coronary heart disease was evaluated in 3 independent studies. Our results showed that the OAZ1+2222A/G polymorphism is consistently associated with all the 3 phenotypes, suggesting an involvement of the polyamine pathway in vascular diseases.

Key Words: ornithine decarboxylase antizyme 1 • gene mutations • coronary in-stent restenosis • common carotid intima-media thickness • coronary heart disease