Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification

Haiqing Shen, Lawrence F. Bielak, Jane F. Ferguson, Elizabeth A. Streeten, Laura M. Yerges-Armstrong, Jie Liu, Wendy Post, Jeffery R. O'Connell, 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 & 3 others Patricia A. Peyser, Muredach P. Reilly, Braxton D. Mitchell

Research output: Contribution to journalArticle

43 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Pages (from-to)2648-2654
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume30
Issue number12
DOIs
StatePublished - Dec 2010
Externally publishedYes

Fingerprint

Vitamin D
Coronary Vessels
Single Nucleotide Polymorphism
Genes
Molecular Epidemiology
Vitamin D3 24-Hydroxylase
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Amish
Endocrine System
X Ray Computed Tomography
Population
Homeostasis
Cardiovascular Diseases
Alleles
Calcium

Keywords

  • calcification
  • coronary artery disease
  • epidemiology
  • gene mutations
  • vitamin D metabolism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Shen, H., Bielak, L. F., Ferguson, J. F., Streeten, E. A., Yerges-Armstrong, L. M., Liu, J., ... Mitchell, B. D. (2010). Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(12), 2648-2654. https://doi.org/10.1161/ATVBAHA.110.211805

Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification. / Shen, Haiqing; Bielak, Lawrence F.; Ferguson, Jane F.; Streeten, Elizabeth A.; Yerges-Armstrong, Laura M.; Liu, Jie; Post, Wendy; O'Connell, 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.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 30, No. 12, 12.2010, p. 2648-2654.

Research output: Contribution to journalArticle

Shen, H, Bielak, LF, Ferguson, JF, Streeten, EA, Yerges-Armstrong, LM, Liu, J, Post, W, O'Connell, JR, Hixson, JE, Kardia, SLR, Sun, YV, Jhun, MA, Wang, X, Mehta, NN, Li, M, Koller, DL, Hakonarson, H, Keating, BJ, Rader, DJ, Shuldiner, AR, Peyser, PA, Reilly, MP & Mitchell, BD 2010, 'Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 12, pp. 2648-2654. https://doi.org/10.1161/ATVBAHA.110.211805
Shen, Haiqing ; Bielak, Lawrence F. ; Ferguson, Jane F. ; Streeten, Elizabeth A. ; Yerges-Armstrong, Laura M. ; Liu, Jie ; Post, Wendy ; O'Connell, 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. / Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2010 ; Vol. 30, No. 12. pp. 2648-2654.
@article{ba389d3a9717446587b2322eca8a322c,
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). 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. 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.",
keywords = "calcification, coronary artery disease, epidemiology, gene mutations, vitamin D metabolism",
author = "Haiqing Shen and Bielak, {Lawrence F.} and Ferguson, {Jane F.} and Streeten, {Elizabeth A.} and Yerges-Armstrong, {Laura M.} and Jie Liu and Wendy Post and O'Connell, {Jeffery R.} and Hixson, {James E.} and Kardia, {Sharon L R} and Sun, {Yan V.} and Jhun, {Min A.} and Xuexia Wang and Mehta, {Nehal N.} and Mingyao Li and Koller, {Daniel L.} and Hakan Hakonarson and Keating, {Brendan J.} and Rader, {Daniel J.} and Shuldiner, {Alan R.} and Peyser, {Patricia A.} and Reilly, {Muredach P.} and Mitchell, {Braxton D.}",
year = "2010",
month = "12",
doi = "10.1161/ATVBAHA.110.211805",
language = "English (US)",
volume = "30",
pages = "2648--2654",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

TY - JOUR

T1 - Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification

AU - Shen, Haiqing

AU - Bielak, Lawrence F.

AU - Ferguson, Jane F.

AU - Streeten, Elizabeth A.

AU - Yerges-Armstrong, Laura M.

AU - Liu, Jie

AU - Post, Wendy

AU - O'Connell, Jeffery R.

AU - Hixson, James E.

AU - Kardia, Sharon L R

AU - Sun, Yan V.

AU - Jhun, Min A.

AU - Wang, Xuexia

AU - Mehta, Nehal N.

AU - Li, Mingyao

AU - Koller, Daniel L.

AU - Hakonarson, Hakan

AU - Keating, Brendan J.

AU - Rader, Daniel J.

AU - Shuldiner, Alan R.

AU - Peyser, Patricia A.

AU - Reilly, Muredach P.

AU - Mitchell, Braxton D.

PY - 2010/12

Y1 - 2010/12

N2 - 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. 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.

AB - 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. 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.

KW - calcification

KW - coronary artery disease

KW - epidemiology

KW - gene mutations

KW - vitamin D metabolism

UR - http://www.scopus.com/inward/record.url?scp=78650415127&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650415127&partnerID=8YFLogxK

U2 - 10.1161/ATVBAHA.110.211805

DO - 10.1161/ATVBAHA.110.211805

M3 - Article

VL - 30

SP - 2648

EP - 2654

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 12

ER -