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)
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Bjork, Anne
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Uppsala Univ, Dept Med Sci, Uppsala, SwedenUppsala Univ, Dept Med Sci, Uppsala, Sweden
Bjork, Anne
[1
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Mellstrom, Dan
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Univ Gothenburg, Inst Med, Dept Internal Med & Clin Nutr, Geriatr Med, Gothenburg, SwedenUppsala Univ, Dept Med Sci, Uppsala, Sweden
Mellstrom, Dan
[2
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Ohlsson, Claes
[3
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Karlsson, Magnus
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Lund Univ, Skane Univ Hosp, Dept Clin Sci & Orthoped Surg, Malmo, SwedenUppsala Univ, Dept Med Sci, Uppsala, Sweden
Karlsson, Magnus
[4
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Mallmin, Hans
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Uppsala Univ, Dept Surg Sci, Uppsala, SwedenUppsala Univ, Dept Med Sci, Uppsala, Sweden
Mallmin, Hans
[5
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Johansson, Gunnar
[6
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Ljunggren, Osten
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Uppsala Univ, Dept Med Sci, Uppsala, SwedenUppsala Univ, Dept Med Sci, Uppsala, Sweden
Ljunggren, Osten
[1
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Kindmark, Andreas
[1
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[1] Uppsala Univ, Dept Med Sci, Uppsala, Sweden
[2] Univ Gothenburg, Inst Med, Dept Internal Med & Clin Nutr, Geriatr Med, Gothenburg, Sweden
[3] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden
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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St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Div, Sydney, NSW 2010, AustraliaSt Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Div, Sydney, NSW 2010, Australia
Center, JR
Nguyen, TV
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机构:St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Div, Sydney, NSW 2010, Australia
Nguyen, TV
Schneider, D
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机构:St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Div, Sydney, NSW 2010, Australia
Schneider, D
Sambrook, PN
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机构:St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Div, Sydney, NSW 2010, Australia
Sambrook, PN
Eisman, JA
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机构:St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Div, Sydney, NSW 2010, Australia
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St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Program, Sydney, NSW 2010, AustraliaSt Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Program, Sydney, NSW 2010, Australia
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Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USAUniv Gothenburg, Inst Med, Sahlgrenska Acad, CBAR, S-41132 Gothenburg, Sweden
机构:
St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Div, Sydney, NSW 2010, AustraliaSt Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Div, Sydney, NSW 2010, Australia
Center, JR
Nguyen, TV
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机构:St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Div, Sydney, NSW 2010, Australia
Nguyen, TV
Schneider, D
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机构:St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Div, Sydney, NSW 2010, Australia
Schneider, D
Sambrook, PN
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机构:St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Div, Sydney, NSW 2010, Australia
Sambrook, PN
Eisman, JA
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机构:St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Div, Sydney, NSW 2010, Australia
机构:
St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Program, Sydney, NSW 2010, AustraliaSt Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Program, Sydney, NSW 2010, Australia
机构:
Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USAUniv Gothenburg, Inst Med, Sahlgrenska Acad, CBAR, S-41132 Gothenburg, Sweden