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Human lipoxygenase pathway gene variation and association with markers of subclinical atherosclerosis in the diabetes heart study

Citation

Burdon, KP and Rudock, ME and Lehtinen, AB and Langefeld, CD and Bowden, DW and Register, TC and Liu, Y and Freedman, BI and Carr, JJ and Hedrick, CC and Rich, SS, Human lipoxygenase pathway gene variation and association with markers of subclinical atherosclerosis in the diabetes heart study, Mediators of Inflammation Article 170153. ISSN 0962-9351 (2010) [Refereed Article]


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Copyright 2010 The Authors-this article is distributed under the terms of the Creative Commons Attribution License (CC BY 3.0 AU)

DOI: doi:10.1155/2010/170153

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 (n = 828) and nondiabetic (n = 170) 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.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Quantitative Genetics (incl. Disease and Trait Mapping Genetics)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Diabetes
Author:Burdon, KP (Associate Professor Kathryn Burdon)
ID Code:91231
Year Published:2010
Web of Science® Times Cited:16
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-05-13
Last Modified:2014-12-17
Downloads:437 View Download Statistics

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