Association of rs780094 in GCKR with metabolic traits and incident diabetes and cardiovascular disease: The ARIC study

Mark Bi, Wen Hong Linda Kao, Eric Boerwinkle, Ron C. Hoogeveen, Laura J. Rasmussen-Torvik, Brad C. Astor, Kari E. North, Josef Coresh, Anna Köttgen

Research output: Contribution to journalArticle

Abstract

Objective: The minor T-allele of rs780094 in the glucokinase regulator gene (GCKR) associates with a number of metabolic traits including higher triglyceride levels and improved glycemic regulation in study populations of mostly European ancestry. Using data from the Atherosclerosis Risk in Communities (ARIC) Study, we sought to replicate these findings, examine them in a large population-based sample of African American study participants, and to investigate independent associations with other metabolic traits in order to determine if variation in GKCR contributes to their observed clustering. In addition, we examined the association of rs780094 with incident diabetes, coronary heart disease (CHD), and stroke over up mean follow-up times of 8, 15, and 15 years, respectively. Research Design and Methods: Race-stratified analyses were conducted among 10,929 white and 3,960 black participants aged 45-64 at baseline assuming an additive genetic model and using linear and logistic regression and Cox proportional hazards models. Results: Previous findings replicated among white participants in multivariable adjusted models: the T-allele of rs780094 was associated with lower fasting glucose (p = 10-7) and insulin levels (p = 10-6), lower insulin resistance (HOMA-IR, p=10-9), less prevalent diabetes (p = 10-6), and higher CRP (p = 10-8), 2-h postprandial glucose (OGTT, p = 10-6), and triglyceride levels (p = 10-31). Moreover, the T-allele was independently associated with higher HDL cholesterol levels (p = 0.022), metabolic syndrome prevalence (p = 0.043), and lower beta-cell function measured as HOMA-B (p = 0.011). Among black participants, the T-allele was associated only with higher triglyceride levels (p = 0.004) and lower insulin levels (p = 0.002) and HOMA-IR (p = 0.013). Prospectively, the T-allele was associated with reduced incidence of diabetes (p = 10-4) among white participants, but not with incidence of CHD or stroke. Conclusions: Our findings indicate rs780094 has independent associations with multiple metabolic traits as well as incident diabetes, but not incident CHD or stroke. The magnitude of association between the SNP and most traits was of lower magnitude among African American compared to white participants.

Original languageEnglish (US)
Article numbere11690
JournalPLoS One
Volume5
Issue number7
DOIs
StatePublished - 2010

Fingerprint

glucokinase
Glucokinase
Regulator Genes
Medical problems
regulator genes
atherosclerosis
cardiovascular diseases
diabetes
Atherosclerosis
Cardiovascular Diseases
Genes
Alleles
alleles
Triglycerides
Coronary Disease
Insulin
Stroke
triacylglycerols
African Americans
stroke

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bi, M., Linda Kao, W. H., Boerwinkle, E., Hoogeveen, R. C., Rasmussen-Torvik, L. J., Astor, B. C., ... Köttgen, A. (2010). Association of rs780094 in GCKR with metabolic traits and incident diabetes and cardiovascular disease: The ARIC study. PLoS One, 5(7), [e11690]. https://doi.org/10.1371/journal.pone.0011690

Association of rs780094 in GCKR with metabolic traits and incident diabetes and cardiovascular disease : The ARIC study. / Bi, Mark; Linda Kao, Wen Hong; Boerwinkle, Eric; Hoogeveen, Ron C.; Rasmussen-Torvik, Laura J.; Astor, Brad C.; North, Kari E.; Coresh, Josef; Köttgen, Anna.

In: PLoS One, Vol. 5, No. 7, e11690, 2010.

Research output: Contribution to journalArticle

Bi, M, Linda Kao, WH, Boerwinkle, E, Hoogeveen, RC, Rasmussen-Torvik, LJ, Astor, BC, North, KE, Coresh, J & Köttgen, A 2010, 'Association of rs780094 in GCKR with metabolic traits and incident diabetes and cardiovascular disease: The ARIC study', PLoS One, vol. 5, no. 7, e11690. https://doi.org/10.1371/journal.pone.0011690
Bi, Mark ; Linda Kao, Wen Hong ; Boerwinkle, Eric ; Hoogeveen, Ron C. ; Rasmussen-Torvik, Laura J. ; Astor, Brad C. ; North, Kari E. ; Coresh, Josef ; Köttgen, Anna. / Association of rs780094 in GCKR with metabolic traits and incident diabetes and cardiovascular disease : The ARIC study. In: PLoS One. 2010 ; Vol. 5, No. 7.
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abstract = "Objective: The minor T-allele of rs780094 in the glucokinase regulator gene (GCKR) associates with a number of metabolic traits including higher triglyceride levels and improved glycemic regulation in study populations of mostly European ancestry. Using data from the Atherosclerosis Risk in Communities (ARIC) Study, we sought to replicate these findings, examine them in a large population-based sample of African American study participants, and to investigate independent associations with other metabolic traits in order to determine if variation in GKCR contributes to their observed clustering. In addition, we examined the association of rs780094 with incident diabetes, coronary heart disease (CHD), and stroke over up mean follow-up times of 8, 15, and 15 years, respectively. Research Design and Methods: Race-stratified analyses were conducted among 10,929 white and 3,960 black participants aged 45-64 at baseline assuming an additive genetic model and using linear and logistic regression and Cox proportional hazards models. Results: Previous findings replicated among white participants in multivariable adjusted models: the T-allele of rs780094 was associated with lower fasting glucose (p = 10-7) and insulin levels (p = 10-6), lower insulin resistance (HOMA-IR, p=10-9), less prevalent diabetes (p = 10-6), and higher CRP (p = 10-8), 2-h postprandial glucose (OGTT, p = 10-6), and triglyceride levels (p = 10-31). Moreover, the T-allele was independently associated with higher HDL cholesterol levels (p = 0.022), metabolic syndrome prevalence (p = 0.043), and lower beta-cell function measured as HOMA-B (p = 0.011). Among black participants, the T-allele was associated only with higher triglyceride levels (p = 0.004) and lower insulin levels (p = 0.002) and HOMA-IR (p = 0.013). Prospectively, the T-allele was associated with reduced incidence of diabetes (p = 10-4) among white participants, but not with incidence of CHD or stroke. Conclusions: Our findings indicate rs780094 has independent associations with multiple metabolic traits as well as incident diabetes, but not incident CHD or stroke. The magnitude of association between the SNP and most traits was of lower magnitude among African American compared to white participants.",
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AU - Hoogeveen, Ron C.

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N2 - Objective: The minor T-allele of rs780094 in the glucokinase regulator gene (GCKR) associates with a number of metabolic traits including higher triglyceride levels and improved glycemic regulation in study populations of mostly European ancestry. Using data from the Atherosclerosis Risk in Communities (ARIC) Study, we sought to replicate these findings, examine them in a large population-based sample of African American study participants, and to investigate independent associations with other metabolic traits in order to determine if variation in GKCR contributes to their observed clustering. In addition, we examined the association of rs780094 with incident diabetes, coronary heart disease (CHD), and stroke over up mean follow-up times of 8, 15, and 15 years, respectively. Research Design and Methods: Race-stratified analyses were conducted among 10,929 white and 3,960 black participants aged 45-64 at baseline assuming an additive genetic model and using linear and logistic regression and Cox proportional hazards models. Results: Previous findings replicated among white participants in multivariable adjusted models: the T-allele of rs780094 was associated with lower fasting glucose (p = 10-7) and insulin levels (p = 10-6), lower insulin resistance (HOMA-IR, p=10-9), less prevalent diabetes (p = 10-6), and higher CRP (p = 10-8), 2-h postprandial glucose (OGTT, p = 10-6), and triglyceride levels (p = 10-31). Moreover, the T-allele was independently associated with higher HDL cholesterol levels (p = 0.022), metabolic syndrome prevalence (p = 0.043), and lower beta-cell function measured as HOMA-B (p = 0.011). Among black participants, the T-allele was associated only with higher triglyceride levels (p = 0.004) and lower insulin levels (p = 0.002) and HOMA-IR (p = 0.013). Prospectively, the T-allele was associated with reduced incidence of diabetes (p = 10-4) among white participants, but not with incidence of CHD or stroke. Conclusions: Our findings indicate rs780094 has independent associations with multiple metabolic traits as well as incident diabetes, but not incident CHD or stroke. The magnitude of association between the SNP and most traits was of lower magnitude among African American compared to white participants.

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