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Mediators of Inflammation
Volume 2010 (2010), Article ID 170153, 9 pages
http://dx.doi.org/10.1155/2010/170153
Research Article

Human Lipoxygenase Pathway Gene Variation and Association with Markers of Subclinical Atherosclerosis in the Diabetes Heart Study

1Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
2Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
3Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
4Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
5Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
6Division of Radiological Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
7Division of Inflammation Biology, La Jolla Institute of Allergy & Immunology, La Jolla, CA 92037, USA
8Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia, P.O. Box 800717, Charlottesville, VA 22908-0717, USA

Received 16 October 2009; Revised 19 January 2010; Accepted 9 March 2010

Academic Editor: Oreste Gualillo

Copyright © 2010 Kathryn P. Burdon et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aims. Genes of the 5-lipoxygenase pathway are compelling candidates for atherosclerosis. We hypothesize that polymorphisms in ALOX12, ALOX15, ALOX5, and ALOX5AP genes are associated with subclinical atherosclerosis in multiple vascular beds. Methods. Families with two or more siblings with type 2 diabetes and their nondiabetic siblings were studied as part of the Diabetes Heart Study (DHS). European American diabetic ( ) and nondiabetic ( ) siblings were genotyped for SNPs in the ALOX12, ALOX15, ALOX5, and ALOX5AP genes. Subclinical measures of atherosclerosis (IMT, coronary (CorCP), carotid (CarCP) and aortic (AorCP) calcified plaque) were obtained. Results. Associations were observed between ALOX12 with CorCP, ALOX5 with CorCP, AorCP, and IMT, and ALOX5AP with CorCP and CarCP, independent of known epidemiologic risk factors. Further, lipoxygenase pathway SNPs that were associated with measures of atherosclerosis were associated with markers of inflammation (CRP, ICAM-1) and calcification (MGP). Conclusions. Polymorphisms within ALOX12, ALOX5, and ALOX5AP are genetically associated with subclinical atherosclerosis and with biomarkers of disease in families with type 2 diabetes. These results suggest that variants in lipoxygenase pathway genes may have pleiotropic effects on multiple components that determine risk of cardiovascular disease.