title: Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification.
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).
  
  
  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.
authors.affiliation: Division of Endocrinology, University of Maryland School of Medicine, Baltimore, Md 21201, USA.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Shen
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Bielak
authors.forename: Jane F
authors.initials: JF
authors.lastname: Ferguson
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Streeten
authors.forename: Laura M
authors.initials: LM
authors.lastname: Yerges-Armstrong
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Wendy
authors.initials: W
authors.lastname: Post
authors.forename: Jeffery R
authors.initials: JR
authors.lastname: O'Connell
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
authors.forename: Sharon L R
authors.initials: SL
authors.lastname: Kardia
authors.forename: Yan V
authors.initials: YV
authors.lastname: Sun
authors.forename: Min A
authors.initials: MA
authors.lastname: Jhun
authors.forename: Xuexia
authors.initials: X
authors.lastname: Wang
authors.forename: Nehal N
authors.initials: NN
authors.lastname: Mehta
authors.forename: Mingyao
authors.initials: M
authors.lastname: Li
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Koller
authors.forename: Hakan
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Keating
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Peyser
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
mesh_terms: 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
chemical_list: 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