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

Burdon KP, Rudock ME, Lehtinen AB, Langefeld CD, Bowden DW, Register TC, Liu Y, Freedman BI, Carr JJ, Hedrick CC, Rich SS
Mediators Inflamm. 2010 2010: 170153

PMID: 20592751 · PMCID: PMC2878676 · DOI:10.1155/2010/170153

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.

MeSH Terms (15)

Aged Animals Arachidonate 5-Lipoxygenase Atherosclerosis Biomarkers Diabetes Mellitus, Type 2 Female Genetic Predisposition to Disease Genetic Variation Genotype Humans Isoenzymes Middle Aged Phenotype Polymorphism, Single Nucleotide

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