Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism.

TitleGenome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism.
Publication TypeJournal Article
Year of Publication2017
AuthorsLi, M, Maruthur, NM, Loomis, SJ, Pietzner, M, North, KE, Mei, H, Morrison, AC, Friedrich, N, Pankow, JS, Nauck, M, Boerwinkle, E, Teumer, A, Selvin, E, Köttgen, A
JournalSci Rep
Date Published2017 Jun 06
KeywordsAged, Black or African American, Deoxyglucose, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose, Glycated Hemoglobin, Humans, Hyperglycemia, Insulin, Male, Middle Aged, Minichromosome Maintenance Complex Component 6, Sodium-Glucose Transporter 1, White People

1,5-anhydroglucitol (1,5-AG) is a biomarker of hyperglycemic excursions associated with diabetic complications. Because of its structural similarity to glucose, genetic studies of 1,5-AG can deliver complementary insights into glucose metabolism. We conducted genome-wide association studies of serum 1,5-AG concentrations in 7,550 European ancestry (EA) and 2,030 African American participants (AA) free of diagnosed diabetes from the ARIC Study. Seven loci in/near EFNA1/SLC50A1, MCM6/LCT, SI, MGAM, MGAM2, SLC5A10, and SLC5A1 showed genome-wide significant associations (P < 5 × 10) among EA participants, five of which were novel. Six of the seven loci were successfully replicated in 8,790 independent EA individuals, and MCM6/LCT and SLC5A10 were also associated among AA. Most of 1,5-AG-associated index SNPs were not associated with the clinical glycemic markers fasting glucose or the  HbA1c, and vice versa. Only the index variant in SLC5A1 showed a significant association with fasting glucose in the expected opposing direction. Products of genes in all 1,5-AG-associated loci have known roles in carbohydrate digestion and enteral or renal glucose transport, suggesting that genetic variants associated with 1,5-AG influence its concentration via effects on glucose metabolism and handling.

Alternate JournalSci Rep
PubMed ID28588231
PubMed Central IDPMC5460207
Grant ListR01 DK089174 / DK / NIDDK NIH HHS / United States
T32 HL007024 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
K24 DK106414 / DK / NIDDK NIH HHS / United States

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