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

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 di...

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Published in:Mediators of Inflammation Vol. 2010; no. 2010; pp. 72 - 80
Main Authors: Freedman, Barry I., Carr, J. Jeffrey, Hedrick, Catherine C., Rich, Stephen S., Burdon, Kathryn P., Liu, Yongmei, Register, Thomas C., Bowden, Donald W., Rudock, Megan E., Lehtinen, Allison B., Langefeld, Carl D.
Format: Journal Article
Language:English
Published: Cairo, Egypt Hindawi Limiteds 01.01.2010
Hindawi Puplishing Corporation
Hindawi Publishing Corporation
John Wiley & Sons, Inc
Wiley
Subjects:
Aged
Animals
Arachidonate 5-Lipoxygenase - genetics
Arachidonate 5-Lipoxygenase - metabolism
Atherosclerosis
Atherosclerosis - genetics
Atherosclerosis - pathology
Atherosclerosis - physiopathology
Biomarkers - metabolism
Development and progression
Diabetes Mellitus, Type 2 - pathology
Diabetes Mellitus, Type 2 - physiopathology
Female
Genetic aspects
Genetic polymorphisms
Genetic Predisposition to Disease
Genetic Variation
Genotype
Health aspects
Humans
Isoenzymes - genetics
Isoenzymes - metabolism
Middle Aged
Oxidases
Phenotype
Polymorphism, Single Nucleotide
United States
ISSN:0962-9351, 1466-1861, 1466-1861
Online Access:Get full text
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Summary: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.
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Academic Editor: Oreste Gualillo
ISSN:0962-9351
1466-1861
1466-1861
DOI:10.1155/2010/170153