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. ShuldinerPatricia A. Peyser, Muredach P. Reilly, Braxton D. Mitchell

Research output: Contribution to journalArticle

44 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.
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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.",
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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.}",
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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

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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

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