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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)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
Univ Gothenburg, Inst Med, Dept Internal Med & Clin Nutr, Geriatr Med, Gothenburg, Sweden.
Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden.ORCID-id: 0000-0002-9633-2805
Lund Univ, Skane Univ Hosp, Dept Clin Sci & Orthoped Surg, Malmo, Sweden.
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2018 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 12, artikkel-id e0209268Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
PUBLIC LIBRARY SCIENCE , 2018. Vol. 13, nr 12, artikkel-id e0209268
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Identifikatorer
URN: urn:nbn:se:uu:diva-373326DOI: 10.1371/journal.pone.0209268ISI: 000454149400035PubMedID: 30576350OAI: oai:DiVA.org:uu-373326DiVA, id: diva2:1278743
Forskningsfinansiär
Swedish Research Council, 2011-2535Tilgjengelig fra: 2019-01-15 Laget: 2019-01-15 Sist oppdatert: 2019-01-15bibliografisk kontrollert

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