Association of the Vitamin D Metabolism Gene CYP24A1 With Coronary Artery Calcification

OBJECTIVE—The vitamin D endocrine system is essential for calcium homeostasis, and low levels of vitamin D metabolites have been associated with cardiovascular disease risk. We hypothesized that DNA sequence variation in genes regulating vitamin D metabolism and signaling pathways might influence va...

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Published in:	Arteriosclerosis, thrombosis, and vascular biology Vol. 30; no. 12; pp. 2648 - 2654
Main Authors:	Shen, Haiqing, Bielak, Lawrence F, Ferguson, Jane F, Streeten, Elizabeth A, Yerges-Armstrong, Laura M, Liu, Jie, Post, Wendy, OʼConnell, Jeffery R, Hixson, James E, Kardia, Sharon L.R, Sun, Yan V, Jhun, Min A, Wang, Xuexia, Mehta, Nehal N, Li, Mingyao, Koller, Daniel L, Hakonarson, Hakan, Keating, Brendan J, Rader, Daniel J, Shuldiner, Alan R, Peyser, Patricia A, Reilly, Muredach P, Mitchell, Braxton D
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Heart Association, Inc 01-12-2010 Lippincott Williams & Wilkins
Subjects:	25-Hydroxyvitamin D3 1-alpha-Hydroxylase - genetics Adult Aged Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Calcinosis - enzymology Calcinosis - ethnology Calcinosis - genetics Cardiology. Vascular system Coronary Artery Disease - enzymology Coronary Artery Disease - ethnology Coronary Artery Disease - genetics Coronary heart disease Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous European Continental Ancestry Group - genetics Female Gene Frequency Genetic Predisposition to Disease Haplotypes Heart Humans Linkage Disequilibrium Male Medical sciences Middle Aged Models, Statistical Phenotype Polymorphism, Single Nucleotide Receptors, Calcitriol - genetics Risk Assessment Risk Factors Steroid Hydroxylases - genetics Steroid Hydroxylases - metabolism United States Vitamin D - metabolism Vitamin D3 24-Hydroxylase coronary artery disease vitamin D metabolism Coronary artery Cardiovascular disease Metabolism Coronary heart disease Epidemiology Vascular disease Vitamin D Atherosclerosis Calcification gene mutations Mutation
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Summary:	OBJECTIVE—The vitamin D endocrine system is essential for calcium homeostasis, and low levels of vitamin D metabolites have been associated with cardiovascular disease risk. We hypothesized that DNA sequence variation in genes regulating vitamin D metabolism and signaling pathways might influence variation in coronary artery calcification (CAC). METHODS AND RESULTS—We genotyped single-nucleotide polymorphisms (SNPs) in GC, CYP27B1, CYP24A1, and VDR and tested their association with CAC quantity, as measured by electron beam computed tomography. Initial association studies were carried out in a discovery sample comprising 697 Amish subjects, and SNPs nominally associated with CAC quantity (4 SNPs in CYP24A1, P=0.008 to 0.00003) were then tested for association with CAC quantity in 2 independent cohorts of subjects of white European ancestry (Genetic Epidemiology Network of Arteriopathy study [n=916] and the Penn Coronary Artery Calcification sample [n=2061]). One of the 4 SNPs, rs2762939, was associated with CAC quantity in both the Genetic Epidemiology Network of Arteriopathy (P=0.007) and Penn Coronary Artery Calcification (P=0.01) studies. In all 3 populations, the rs2762939 C allele was associated with lower CAC quantity. Metaanalysis for the association of this SNP with CAC quantity across all 3 studies yielded a P value of 2.9×10. CONCLUSION—A common SNP in the CYP24A1 gene was associated with CAC quantity in 3 independent populations. This result suggests a role for vitamin D metabolism in the development of CAC quantity.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	1079-5642 1524-4636 1524-4636
DOI:	10.1161/ATVBAHA.110.211805