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 variation in coronary artery calcification (CAC).


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.
Shen
Haiqing
H
Division of Endocrinology, University of Maryland School of Medicine, Baltimore, Md 21201, USA.
Bielak
Lawrence F
LF
Ferguson
Jane F
JF
Streeten
Elizabeth A
EA
Yerges-Armstrong
Laura M
LM
Liu
Jie
J
Post
Wendy
W
O'Connell
Jeffery R
JR
Hixson
James E
JE
Kardia
Sharon L R
SL
Sun
Yan V
YV
Jhun
Min A
MA
Wang
Xuexia
X
Mehta
Nehal N
NN
Li
Mingyao
M
Koller
Daniel L
DL
Hakonarson
Hakan
H
Keating
Brendan J
BJ
Rader
Daniel J
DJ
Shuldiner
Alan R
AR
Peyser
Patricia A
PA
Reilly
Muredach P
MP
Mitchell
Braxton D
BD
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000328:Adult; D000368:Aged; D002114:Calcinosis / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D003324:Coronary Artery Disease / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D014481:United States; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase; D044465:White People / Q000235:genetics
D018167:Receptors, Calcitriol; D014807:Vitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase