Genome-Wide Association Study of Serum Fructosamine and Glycated Albumin in Adults Without Diagnosed Diabetes: Results From the Atherosclerosis Risk in Communities Study.

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  • Additional Information
    • Source:
      Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE
    • Publication Information:
      Publication: Alexandria, VA : American Diabetes Association
      Original Publication: [New York, American Diabetes Association]
    • Subject Terms:
      Genetic Variation*; Adaptor Proteins, Signal Transducing/*genetics ; Atherosclerosis/*genetics ; Calcium-Binding Proteins/*genetics ; Diabetes Mellitus, Type 2/*genetics ; Fructosamine/*blood ; Serum Albumin/*analysis; Adaptor Proteins, Signal Transducing/metabolism ; Adult ; Black or African American ; Atherosclerosis/blood ; Atherosclerosis/metabolism ; Biomarkers/blood ; Calcium-Binding Proteins/metabolism ; Cohort Studies ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/metabolism ; Female ; Genetic Markers ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Glycation End Products, Advanced ; Humans ; Male ; Middle Aged ; Mutation, Missense ; Polymorphism, Single Nucleotide ; Prospective Studies ; Reproducibility of Results ; United States ; White People ; Glycated Serum Albumin
    • Abstract:
      Fructosamine and glycated albumin are potentially useful alternatives to hemoglobin A 1c (HbA 1c ) as diabetes biomarkers. The genetic determinants of fructosamine and glycated albumin, however, are unknown. We performed genome-wide association studies of fructosamine and glycated albumin among 2,104 black and 7,647 white participants without diabetes in the Atherosclerosis Risk in Communities (ARIC) Study and replicated findings in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Among whites, rs34459162, a novel missense single nucleotide polymorphism (SNP) in RCN3 , was associated with fructosamine ( P = 5.3 × 10 -9 ) and rs1260236, a known diabetes-related missense mutation in GCKR , was associated with percent glycated albumin ( P = 5.9 × 10 -9 ) and replicated in CARDIA. We also found two novel associations among blacks: an intergenic SNP, rs2438321, associated with fructosamine ( P = 6.2 × 10 -9 ), and an intronic variant in PRKCA , rs59443763, associated with percent glycated albumin ( P = 4.1 × 10 -9 ), but these results did not replicate. Few established fasting glucose or HbA 1c SNPs were also associated with fructosamine or glycated albumin. Overall, we found genetic variants associated with the glycemic information captured by fructosamine and glycated albumin as well as with their nonglycemic component. This highlights the importance of examining the genetics of hyperglycemia biomarkers to understand the information they capture, including potential glucose-independent factors.
      (© 2018 by the American Diabetes Association.)
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    • Grant Information:
      N01 HC065226 United States HL NHLBI NIH HHS; HHSN268201300026C United States HL NHLBI NIH HHS; U01 HG004446 United States HG NHGRI NIH HHS; UL1 RR025005 United States RR NCRR NIH HHS; R01 HL086694 United States HL NHLBI NIH HHS; U01 HG004729 United States HG NHGRI NIH HHS; HHSN268201700001I United States HL NHLBI NIH HHS; N01HC65226 United States HL NHLBI NIH HHS; M01 RR000032 United States RR NCRR NIH HHS; K01 DK095928 United States DK NIDDK NIH HHS; HHSN268201700004C United States HL NHLBI NIH HHS; HHSN268201700003I United States HL NHLBI NIH HHS; R01 DK089174 United States DK NIDDK NIH HHS; UL1 TR000165 United States TR NCATS NIH HHS; T32 HL007024 United States HL NHLBI NIH HHS; P30 DK079626 United States DK NIDDK NIH HHS; U01 HG004402 United States HG NHGRI NIH HHS; U01 HG004424 United States HG NHGRI NIH HHS; HHSN268201300025C United States HL NHLBI NIH HHS; HHSN268201300027C United States HL NHLBI NIH HHS; HHSN268201700002C United States HL NHLBI NIH HHS; HHSN268200900041C United States HL NHLBI NIH HHS; HHSN268201300028C United States HL NHLBI NIH HHS; K24 DK106414 United States DK NIDDK NIH HHS; HHSN268201700004I United States HL NHLBI NIH HHS; HHSN268201700005C United States HL NHLBI NIH HHS; HHSN268201700001C United States HL NHLBI NIH HHS; HHSN268201700003C United States HL NHLBI NIH HHS; UL1 TR001417 United States TR NCATS NIH HHS; HHSN268201700002I United States HL NHLBI NIH HHS; HHSN268201700005I United States HL NHLBI NIH HHS; HHSN268201300029C United States HL NHLBI NIH HHS; R01 HL087641 United States HL NHLBI NIH HHS
    • Accession Number:
      0 (Adaptor Proteins, Signal Transducing)
      0 (Biomarkers)
      0 (Calcium-Binding Proteins)
      0 (GCKR protein, human)
      0 (Genetic Markers)
      0 (Glycation End Products, Advanced)
      0 (RCN3 protein, human)
      0 (Serum Albumin)
      4429-04-3 (Fructosamine)
      0 (Glycated Serum Albumin)
    • Publication Date:
      Date Created: 20180531 Date Completed: 20180727 Latest Revision: 20240610
    • Publication Date:
      20240610
    • Accession Number:
      PMC6054442
    • Accession Number:
      10.2337/db17-1362
    • Accession Number:
      29844224