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

TitleGenome-Wide Association Study of Serum Fructosamine and Glycated Albumin in Adults Without Diagnosed Diabetes: Results From the Atherosclerosis Risk in Communities Study.
Publication TypeJournal Article
Year of Publication2018
AuthorsLoomis SJ, Li M, Maruthur NM, Baldridge AS, North KE, Mei H, Morrison A, Carson AP, Pankow JS, Boerwinkle E, Scharpf R, Rasmussen-Torvik LJ, Coresh JJ, Duggal P, Köttgen A
Secondary AuthorsSelvin E
JournalDiabetes
Volume67
Issue8
Pagination1684-1696
Date Published2018 08
ISSN1939-327X
KeywordsAdaptor Proteins, Signal Transducing, Adult, African Americans, Atherosclerosis, Biomarkers, Calcium-Binding Proteins, Cohort Studies, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Fructosamine, Genetic Markers, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Male, Middle Aged, Mutation, Missense, Polymorphism, Single Nucleotide, Prospective Studies, Reproducibility of Results, Serum Albumin, United States
Abstract

Fructosamine and glycated albumin are potentially useful alternatives to hemoglobin A (HbA) 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 , was associated with fructosamine ( = 5.3 × 10) and rs1260236, a known diabetes-related missense mutation in , was associated with percent glycated albumin ( = 5.9 × 10) and replicated in CARDIA. We also found two novel associations among blacks: an intergenic SNP, rs2438321, associated with fructosamine ( = 6.2 × 10), and an intronic variant in , rs59443763, associated with percent glycated albumin ( = 4.1 × 10), but these results did not replicate. Few established fasting glucose or HbA 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.

DOI10.2337/db17-1362
Alternate JournalDiabetes
PubMed ID29844224
PubMed Central IDPMC6054442
Grant ListHHSN268201300026C / HL / NHLBI NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
R01 DK089174 / DK / NIDDK NIH HHS / United States
UL1 TR000165 / TR / NCATS NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
T32 HL007024 / HL / NHLBI NIH HHS / United States
P30 DK079626 / DK / NIDDK NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
U01 HG004424 / HG / NHGRI NIH HHS / United States
HHSN268201300025C / HL / NHLBI NIH HHS / United States
N01 HC065226 / NHLBI NIH HHS / Division of Epidemiology & Clinical Applications / United States
U01 HG004729 / HG / NHGRI NIH HHS / United States
HHSN268201300027C / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268200900041C / HL / NHLBI NIH HHS / United States
HHSN268201300028C / HL / NHLBI NIH HHS / United States
K24 DK106414 / DK / NIDDK NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
N01HC65226 / HL / NHLBI NIH HHS / United States
M01 RR000032 / RR / NCRR NIH HHS / United States
K01 DK095928 / DK / NIDDK NIH HHS / United States
UL1 TR001417 / TR / NCATS NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
HHSN268201300029C / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States