Genome-wide association study of serum fructosamine and glycated albumin in adults without diagnosed diabetes

Results from the atherosclerosis risk in communities study

Stephanie J. Loomis, Man Li, Nisa M. Maruthur, Abigail S. Baldridge, Kari E. North, Hao Mei, Alanna Morrison, April P. Carson, James S. Pankow, Eric Boerwinkle, Robert Scharpf, Laura J. Rasmussen-Torvik, Josef Coresh, Priya Duggal, Anna Köttgen, Elizabeth Selvin

Research output: Contribution to journalArticle

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Abstract

Fructosamine and glycated albumin are potentially useful alternatives to hemoglobin A1c (HbA1c) 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 3 1029) and rs1260236, a known diabetes-related missense mutation in GCKR, was associated with percent glycated albumin (P = 5.9 3 1029) and replicated in CARDIA. We also found two novel associations among blacks: an intergenic SNP, rs2438321, associated with fructosamine (P = 6.2 3 1029), and an intronic variant in PRKCA, rs59443763, associated with percent glycated albumin (P = 4.1 3 1029), but these results did not replicate. Few established fasting glucose or HbA1c 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.

Original languageEnglish (US)
Pages (from-to)1684-1696
Number of pages13
JournalDiabetes
Volume67
Issue number8
DOIs
StatePublished - Aug 1 2018

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Fructosamine
Genome-Wide Association Study
Serum Albumin
Atherosclerosis
Single Nucleotide Polymorphism
Young Adult
Coronary Vessels
Hemoglobins
Biomarkers
Glucose
Missense Mutation
glycosylated serum albumin
Hyperglycemia
Fasting

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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. / Loomis, Stephanie J.; Li, Man; Maruthur, Nisa M.; Baldridge, Abigail S.; North, Kari E.; Mei, Hao; Morrison, Alanna; Carson, April P.; Pankow, James S.; Boerwinkle, Eric; Scharpf, Robert; Rasmussen-Torvik, Laura J.; Coresh, Josef; Duggal, Priya; Köttgen, Anna; Selvin, Elizabeth.

In: Diabetes, Vol. 67, No. 8, 01.08.2018, p. 1684-1696.

Research output: Contribution to journalArticle

Loomis, 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, J, Duggal, P, Köttgen, A & Selvin, E 2018, 'Genome-wide association study of serum fructosamine and glycated albumin in adults without diagnosed diabetes: Results from the atherosclerosis risk in communities study', Diabetes, vol. 67, no. 8, pp. 1684-1696. https://doi.org/10.2337/db17-1362
Loomis, Stephanie J. ; Li, Man ; Maruthur, Nisa M. ; Baldridge, Abigail S. ; North, Kari E. ; Mei, Hao ; Morrison, Alanna ; Carson, April P. ; Pankow, James S. ; Boerwinkle, Eric ; Scharpf, Robert ; Rasmussen-Torvik, Laura J. ; Coresh, Josef ; Duggal, Priya ; Köttgen, Anna ; Selvin, Elizabeth. / Genome-wide association study of serum fructosamine and glycated albumin in adults without diagnosed diabetes : Results from the atherosclerosis risk in communities study. In: Diabetes. 2018 ; Vol. 67, No. 8. pp. 1684-1696.
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abstract = "Fructosamine and glycated albumin are potentially useful alternatives to hemoglobin A1c (HbA1c) 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 3 1029) and rs1260236, a known diabetes-related missense mutation in GCKR, was associated with percent glycated albumin (P = 5.9 3 1029) and replicated in CARDIA. We also found two novel associations among blacks: an intergenic SNP, rs2438321, associated with fructosamine (P = 6.2 3 1029), and an intronic variant in PRKCA, rs59443763, associated with percent glycated albumin (P = 4.1 3 1029), but these results did not replicate. Few established fasting glucose or HbA1c 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.",
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AU - Li, Man

AU - Maruthur, Nisa M.

AU - Baldridge, Abigail S.

AU - North, Kari E.

AU - Mei, Hao

AU - Morrison, Alanna

AU - Carson, April P.

AU - Pankow, James S.

AU - Boerwinkle, Eric

AU - Scharpf, Robert

AU - Rasmussen-Torvik, Laura J.

AU - Coresh, Josef

AU - Duggal, Priya

AU - Köttgen, Anna

AU - Selvin, Elizabeth

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N2 - Fructosamine and glycated albumin are potentially useful alternatives to hemoglobin A1c (HbA1c) 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 3 1029) and rs1260236, a known diabetes-related missense mutation in GCKR, was associated with percent glycated albumin (P = 5.9 3 1029) and replicated in CARDIA. We also found two novel associations among blacks: an intergenic SNP, rs2438321, associated with fructosamine (P = 6.2 3 1029), and an intronic variant in PRKCA, rs59443763, associated with percent glycated albumin (P = 4.1 3 1029), but these results did not replicate. Few established fasting glucose or HbA1c 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.

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