Association of polymorphisms in cyclooxygenase (COX)-2 with coronary and carotid calcium in the Diabetes Heart Study

Cardiovascular disease is the leading cause of death among Americans. Inflammation is a hallmark of the development of atherosclerosis and is mediated by prostaglandins, catalyzed by cyclooxygenase (COX)-2. We sought to determine if variants in the COX-2 gene were associated with subclinical measure...

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Published in:Atherosclerosis Vol. 203; no. 2; pp. 459 - 465
Main Authors: Rudock, Megan E., Liu, Yongmei, Ziegler, Julie T., Allen, Stewart G., Lehtinen, Allison B., Freedman, Barry I., Carr, J. Jeffrey, Langefeld, Carl D., Bowden, Donald W.
Format: Journal Article
Language:English
Published: Amsterdam Elsevier Ireland Ltd 01.04.2009
Elsevier
Subjects:
Aged
Alleles
Associated diseases and complications
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Calcium - metabolism
Cardiology. Vascular system
Cardiovascular
Cardiovascular disease
Carotid Arteries - metabolism
Coronary Vessels - metabolism
Cyclooxygenase
Cyclooxygenase 2 - biosynthesis
Cyclooxygenase 2 - genetics
Diabetes Complications
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - metabolism
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Family Health
Female
Genomics
Genotype
Humans
Inflammation
Male
Medical sciences
Middle Aged
Models, Statistical
Polymorphism, Genetic
Polymorphisms
Type 2 diabetes mellitus
Vascular calcification
Vascular calcification
Cardiovascular disease
Cyclooxygenase
Inflammation
Type 2 diabetes mellitus
Polymorphisms
Endocrinopathy
Type 2 diabetes
Prostaglandin-endoperoxide synthase
Calcium
Enzyme
Metabolic diseases
Inorganic element
Coronary heart disease
Artery
Vascular disease
Blood vessel
Carotid
Atherosclerosis
Calcification
Circulatory system
Oxidoreductases
Polymorphism
ISSN:0021-9150, 1879-1484, 1879-1484
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Summary:Cardiovascular disease is the leading cause of death among Americans. Inflammation is a hallmark of the development of atherosclerosis and is mediated by prostaglandins, catalyzed by cyclooxygenase (COX)-2. We sought to determine if variants in the COX-2 gene were associated with subclinical measures of cardiovascular disease in a primarily type 2 diabetic population. Eight polymorphisms in COX-2 were genotyped and vascular calcified plaque measured in the coronary, carotid, and aortic arterial beds in 977 Caucasian siblings (83% with T2DM) from 369 Diabetes Heart Study families. Tests for single nucleotide polymorphism (SNP) and haplotypic association were performed using SOLAR and quantitative pedigree disequilibrium test (QPDT), respectively (results adjusted for age, gender, diabetes affection status, smoking, and use of lipid altering medications). All eight SNPs genotyped were found to be in strong pair-wise linkage disequilibrium ( D′ = 1.0). Three SNPs (rs689466, rs2066826 and rs20417) are associated with either coronary or carotid calcified plaque. Subjects carrying the G allele of rs689466 ( n = 31) or the A allele of rs2066826 ( n = 16) had significantly lower coronary calcified plaque ( P = 0.02 and 0.04, respectively). Subjects homozygous for the C allele of rs20417 ( n = 22) or the A allele of rs2066826 ( n = 16) had increased carotid calcified plaque ( P = 0.011, P = 0.014). In addition, multiple two-SNP and three-SNP haplotypes were associated with CorCP with P-values ranging from P = 0.002 to P = 0.035. Polymorphisms in COX-2 were associated with significant changes in coronary and carotid calcified plaque. Diabetic individuals with these variants may be at higher risk for developing cardiovascular disease.
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ISSN:0021-9150
1879-1484
1879-1484
DOI:10.1016/j.atherosclerosis.2008.07.018