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Genetic Variants Associated with Circulating Fibroblast Growth Factor 23.

TitleGenetic Variants Associated with Circulating Fibroblast Growth Factor 23.
Publication TypeJournal Article
Year of Publication2018
AuthorsRobinson-Cohen C, Bartz TM, Lai D, T Ikizler A, Peacock M, Imel EA, Michos ED, Foroud TM, Akesson K, Taylor KD, Malmgren L, Matsushita K, Nethander M, Eriksson J, Ohlsson C, Mellström D, Wolf M, Ljunggren O, McGuigan F, Rotter JI, Karlsson M, Econs MJ, Ix JH, Lutsey PL, Psaty BM, de Boer IH
Secondary AuthorsKestenbaum BR
JournalJ Am Soc Nephrol
Volume29
Issue10
Pagination2583-2592
Date Published2018 10
ISSN1533-3450
KeywordsAfrican Continental Ancestry Group, Cohort Studies, European Continental Ancestry Group, Female, Fibroblast Growth Factors, Genome-Wide Association Study, Humans, Kidney, Male, Phosphates, Polymorphism, Single Nucleotide, RGS Proteins, Sodium-Phosphate Cotransporter Proteins, Type IIa, Vitamin D, Vitamin D3 24-Hydroxylase
Abstract

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

RESULTS: We discovered 154 SNPs from five independent regions associated with FGF23 concentration. The SNP with the strongest association, rs17216707 (=3.0×10), lies upstream of , 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 and upstream of (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 , 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.

DOI10.1681/ASN.2018020192
Alternate JournalJ Am Soc Nephrol
PubMed ID30217807
PubMed Central IDPMC6171267
Grant ListHHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
U01 AG027810 / AG / NIA NIH HHS / United States
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R01 HL103612 / HL / NHLBI NIH HHS / United States
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P30 AR072581 / AR / NIAMS NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
R01 HL103706 / HL / NHLBI NIH HHS / United States
UL1 RR025761 / RR / NCRR NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
R01 HL071251 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
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