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Association of rs780094 in GCKR with Metabolic Traits and Incident Diabetes and Cardiovascular Disease: The ARIC Study

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 Communit...

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Autores principales: Bi, Mark, Kao, Wen Hong Linda, Boerwinkle, Eric, Hoogeveen, Ron C., Rasmussen-Torvik, Laura J., Astor, Brad C., North, Kari E., Coresh, Josef, Köttgen, Anna
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908550/
https://www.ncbi.nlm.nih.gov/pubmed/20661421
http://dx.doi.org/10.1371/journal.pone.0011690
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author Bi, Mark
Kao, Wen Hong Linda
Boerwinkle, Eric
Hoogeveen, Ron C.
Rasmussen-Torvik, Laura J.
Astor, Brad C.
North, Kari E.
Coresh, Josef
Köttgen, Anna
author_facet Bi, Mark
Kao, Wen Hong Linda
Boerwinkle, Eric
Hoogeveen, Ron C.
Rasmussen-Torvik, Laura J.
Astor, Brad C.
North, Kari E.
Coresh, Josef
Köttgen, Anna
author_sort Bi, Mark
collection PubMed
description 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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spelling pubmed-29085502010-07-26 Association of rs780094 in GCKR with Metabolic Traits and Incident Diabetes and Cardiovascular Disease: The ARIC Study Bi, Mark Kao, Wen Hong Linda Boerwinkle, Eric Hoogeveen, Ron C. Rasmussen-Torvik, Laura J. Astor, Brad C. North, Kari E. Coresh, Josef Köttgen, Anna PLoS One Research Article 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. Public Library of Science 2010-07-22 /pmc/articles/PMC2908550/ /pubmed/20661421 http://dx.doi.org/10.1371/journal.pone.0011690 Text en Bi et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bi, Mark
Kao, Wen Hong Linda
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
title Association of rs780094 in GCKR with Metabolic Traits and Incident Diabetes and Cardiovascular Disease: The ARIC Study
title_full Association of rs780094 in GCKR with Metabolic Traits and Incident Diabetes and Cardiovascular Disease: The ARIC Study
title_fullStr Association of rs780094 in GCKR with Metabolic Traits and Incident Diabetes and Cardiovascular Disease: The ARIC Study
title_full_unstemmed Association of rs780094 in GCKR with Metabolic Traits and Incident Diabetes and Cardiovascular Disease: The ARIC Study
title_short Association of rs780094 in GCKR with Metabolic Traits and Incident Diabetes and Cardiovascular Disease: The ARIC Study
title_sort association of rs780094 in gckr with metabolic traits and incident diabetes and cardiovascular disease: the aric study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908550/
https://www.ncbi.nlm.nih.gov/pubmed/20661421
http://dx.doi.org/10.1371/journal.pone.0011690
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