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Haplotypes in the CYP2R1 gene are associated with levels of 25(OH)D and bone mineral density, but not with other markers of bone metabolism (MrOS Sweden)

Björk, Anne LU ; Mellström, Dan; Ohlsson, Claes; Karlsson, Magnus LU ; Mallmin, Hans; Johansson, Gunnar; Ljunggren, Östen and Kindmark, Andreas (2018) In PLoS ONE 13(12).
Abstract

Objective Polymorphisms in the CYP2R1 gene encoding Vitamin D 25-hydroxylase have been reported to correlate with circulating levels of 25-OH vitamin D3 (25(OH)D). It is unknown whether these variations also affect overall bone metabolism. In order to elucidate the overall associations of polymorphisms in the CYP2R1, we studied haplotype tagging single nucleotide polymorphisms (SNPs) in the gene and serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23), as well as bone mineral density (BMD). Methods Baseline data on serum parameters and BMD from MrOS Sweden, a prospective population-based cohort study of elderly men (mean age 75 years, range 69–81), were analyzed. Genotyping was... (More)

Objective Polymorphisms in the CYP2R1 gene encoding Vitamin D 25-hydroxylase have been reported to correlate with circulating levels of 25-OH vitamin D3 (25(OH)D). It is unknown whether these variations also affect overall bone metabolism. In order to elucidate the overall associations of polymorphisms in the CYP2R1, we studied haplotype tagging single nucleotide polymorphisms (SNPs) in the gene and serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23), as well as bone mineral density (BMD). Methods Baseline data on serum parameters and BMD from MrOS Sweden, a prospective population-based cohort study of elderly men (mean age 75 years, range 69–81), were analyzed. Genotyping was performed for eight SNPs covering the CYP2R1 gene in 2868 men with available samples of DNA. Subjects were followed up concerning incidence of fracture during five years. Results There was a significant genetic association with circulating levels of 25(OH)D (4.6–18.5% difference in mean values between SNP alleles), but there were no correlations with levels of calcium, phosphate, PTH or FGF23 for any genetic variant. No differences were found in fracture incidence between the variants. There was an inverse relationship between lower BMD and concomitant higher 25(OH)D for three of the haplotypes (p < 0.005). Conclusions Common variants in the CYP2R1 gene encoding Vitamin D 25-hydroxylase correlate with levels of circulating 25(OH)D but do not otherwise associate with measures of calcium and phosphate homeostasis. Presence of the specific haplotypes may be an indicator of risk for low 25(OH)D levels, and may in addition be correlated to bone mineral density.

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published
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in
PLoS ONE
volume
13
issue
12
publisher
Public Library of Science
external identifiers
  • scopus:85058914627
ISSN
1932-6203
DOI
10.1371/journal.pone.0209268
language
English
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yes
id
0e2ddfb3-5e78-43d7-b687-7bba87ebd3bf
date added to LUP
2019-01-04 07:53:37
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2019-02-20 11:41:29
@article{0e2ddfb3-5e78-43d7-b687-7bba87ebd3bf,
  abstract     = {<p>Objective Polymorphisms in the CYP2R1 gene encoding Vitamin D 25-hydroxylase have been reported to correlate with circulating levels of 25-OH vitamin D3 (25(OH)D). It is unknown whether these variations also affect overall bone metabolism. In order to elucidate the overall associations of polymorphisms in the CYP2R1, we studied haplotype tagging single nucleotide polymorphisms (SNPs) in the gene and serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23), as well as bone mineral density (BMD). Methods Baseline data on serum parameters and BMD from MrOS Sweden, a prospective population-based cohort study of elderly men (mean age 75 years, range 69–81), were analyzed. Genotyping was performed for eight SNPs covering the CYP2R1 gene in 2868 men with available samples of DNA. Subjects were followed up concerning incidence of fracture during five years. Results There was a significant genetic association with circulating levels of 25(OH)D (4.6–18.5% difference in mean values between SNP alleles), but there were no correlations with levels of calcium, phosphate, PTH or FGF23 for any genetic variant. No differences were found in fracture incidence between the variants. There was an inverse relationship between lower BMD and concomitant higher 25(OH)D for three of the haplotypes (p &lt; 0.005). Conclusions Common variants in the CYP2R1 gene encoding Vitamin D 25-hydroxylase correlate with levels of circulating 25(OH)D but do not otherwise associate with measures of calcium and phosphate homeostasis. Presence of the specific haplotypes may be an indicator of risk for low 25(OH)D levels, and may in addition be correlated to bone mineral density.</p>},
  articleno    = {e0209268},
  author       = {Björk, Anne and Mellström, Dan and Ohlsson, Claes and Karlsson, Magnus and Mallmin, Hans and Johansson, Gunnar and Ljunggren, Östen and Kindmark, Andreas},
  issn         = {1932-6203},
  language     = {eng},
  month        = {12},
  number       = {12},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Haplotypes in the CYP2R1 gene are associated with levels of 25(OH)D and bone mineral density, but not with other markers of bone metabolism (MrOS Sweden)},
  url          = {http://dx.doi.org/10.1371/journal.pone.0209268},
  volume       = {13},
  year         = {2018},
}