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  • Robinson-Cohen, CassianneVanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, Nashville, TN 37232 USA,Vanderbilt University Medical Center (författare)

Genetic Variants Associated with Circulating Fibroblast Growth Factor 23

  • Artikel/kapitelEngelska2018

Förlag, utgivningsår, omfång ...

  • AMER SOC NEPHROLOGY,2018
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-369511
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-369511URI
  • https://doi.org/10.1681/ASN.2018020192DOI
  • https://lup.lub.lu.se/record/0bfc1565-faab-4d8f-981d-859315beaf01URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Background: Fibroblast growth factor 23 (FGF23), a bone-derived hormone that regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of mineral and bone disorders in CKD and is an emerging cardiovascular risk factor. Central elements of FGF23 regulation remain incompletely understood; genetic variation may help explain interindividual differences.Methods: We performed a meta-analysis of genome-wide association studies of circulating FGF23 concentrations among 16,624 participants of European ancestry from seven cohort studies, excluding participants with eGFR<30 ml/min per 1.73 m(2) to focus on FGF23 under normal conditions. We evaluated the association of single-nucleotide polymorphisms (SNPs) with natural log-transformed FGF23 concentration, adjusted for age, sex, study site, and principal components of ancestry. A second model additionally adjusted for BMI and eGFR.Results: We discovered 154 SNPs from five independent regions associated with FGF23 concentration. The SNP with the strongest association, rs17216707 (P=3.0x10(-24)), lies upstream of CYP24A1, which encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Each additional copy of the T allele at this locus is associated with 5% higher FGF23 concentration. Another locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport). Additional adjustment for BMI and eGFR did not materially alter the magnitude of these associations. Another top locus (within ABO, the ABO blood group transferase gene) was no longer statistically significant at the genome-wide level.Conclusions: Common genetic variants located near genes involved in vitamin D metabolism and renal phosphate transport are associated with differences in circulating FGF23 concentrations.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Bartz, Traci M.Univ Washington, Cardiovasc Hlth Res Unit, Dept Biostat, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA,University of Washington, Seattle (författare)
  • Lai, DongbingIndiana Univ, Dept Med, Indianapolis, IN 46204 USA;Indiana Univ, Dept Mol Genet, Indianapolis, IN 46204 USA,Indiana University (författare)
  • Ikizler, T. AlpVanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, Nashville, TN 37232 USA,Vanderbilt University Medical Center (författare)
  • Peacock, MunroIndiana University (författare)
  • Imel, Erik A.Indiana University (författare)
  • Michos, Erin D.Johns Hopkins Sch Med, Div Cardiol, Baltimore, MD USA,Johns Hopkins University School of Medicine (författare)
  • Foroud, Tatiana M.Indiana Univ, Dept Med, Indianapolis, IN 46204 USA;Indiana Univ, Dept Mol Genet, Indianapolis, IN 46204 USA,Indiana University (författare)
  • Akesson, KristinaLund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)orto-kak (författare)
  • Taylor, Kent D.Harbor Univ Calif, Los Angeles Med Ctr, Los Angeles Biomed Res Inst Harbor, Dept Pediat,Inst Translat Gen & Populat Sci, Torrance, CA USA,University of California, Los Angeles (författare)
  • Malmgren, LinneaLund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-lam (författare)
  • Matsushita, KunihiroJohns Hopkins Sch Med, Div Cardiol, Baltimore, MD USA;Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA,Johns Hopkins University (författare)
  • Nethander, MariaUniversity of Gothenburg (författare)
  • Eriksson, JoelUniversity of Gothenburg (författare)
  • Ohlsson, ClaesUniversity of Gothenburg (författare)
  • Mellström, DanielUniversity of Gothenburg (författare)
  • Wolf, MylesDuke Univ, Sch Med, Div Nephrol, Dept Med, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA,Duke University (författare)
  • Ljunggren, ÖstenUppsala University,Uppsala universitet,Endokrinologi och mineralmetabolism(Swepub:uu)osteljun (författare)
  • McGuigan, FionaLund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-fam (författare)
  • Rotter, Jerome I.Harbor Univ Calif, Los Angeles Med Ctr, Los Angeles Biomed Res Inst Harbor, Dept Pediat,Inst Translat Gen & Populat Sci, Torrance, CA USA,University of California System (författare)
  • Karlsson, MagnusLund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)orto-mka (författare)
  • Econs, Michael J.Indiana Univ, Dept Med, Indianapolis, IN 46204 USA;Indiana Univ, Dept Mol Genet, Indianapolis, IN 46204 USA,Indiana University (författare)
  • Ix, Joachim H.Univ Calif San Diego, Dept Med, Div Nephrol Hypertens, San Diego, CA 92103 USA;Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA,University of California, San Diego (författare)
  • Lutsey, Pamela L.Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA,University of Minnesota (författare)
  • Psaty, Bruce M.Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente, Washington Hlth Res Inst, Seattle, WA USA,Kaiser Permanente Research Institute,University of Washington, Seattle (författare)
  • de Boer, Ian H.Univ Washington, Kidney Res Inst, Div Nephrol, Dept Med, Seattle, WA 98195 USA,University of Washington, Seattle (författare)
  • Kestenbaum, Bryan R.Univ Washington, Kidney Res Inst, Div Nephrol, Dept Med, Seattle, WA 98195 USA,University of Washington, Seattle (författare)
  • Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, Nashville, TN 37232 USAVanderbilt University Medical Center (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of the American Society of Nephrology: AMER SOC NEPHROLOGY29:10, s. 2583-25921046-66731533-3450

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