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

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2010 Sep 18

PMID 20847308

Citations 30

Authors

Haiqing Shen

Lawrence F Bielak

Jane F Ferguson

Elizabeth A Streeten

Laura M Yerges-Armstrong

Jie Liu

Wendy Post

Jeffery R Oconnell

James E Hixson

Sharon L R Kardia

Yan V Sun

Min A Jhun

Xuexia Wang

Nehal N Mehta

Mingyao Li

Daniel L Koller

Hakan Hakonarson

Brendan J Keating

Daniel J Rader

Alan R Shuldiner

Patricia A Peyser

Muredach P Reilly

Braxton D Mitchell

Affiliations

Soon will be listed here.

Abstract

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(-6).

Conclusions: 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.

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