ArticleDiabetologia2014
Common genetic variation in the glucokinase gene (GCK) is associated with type 2 diabetes and rates of carbohydrate oxidation and energy expenditure.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 34 citations in OpenAlex.
- Polygenic score from MODY genes is associated with type 1 diabetes and disease characteristics.Acta diabetologica · 2025Article
- The Abundance of Harmful Rare Homozygous Variants in Children of Consanguineous Parents.Biology · 2025Article
- In silico design of dehydrophenylalanine containing peptide activators of glucokinase using pharmacophore modelling, molecular dynamics and machine learning: implications in type 2 diabetes.Journal of computer-aided molecular design · 2024Article
- Potential impact ofMolecular medicine reports · 2022Article
- Gene polymorphisms of insulin secretion signaling pathway associated with clopidogrel resistance in Han Chinese population.Journal of clinical laboratory analysis · 2021Article
- The association of the glucokinase rs4607517 polymorphism with gestational diabetes mellitus and its interaction with sweets consumption in Chinese women.Public health nutrition · 2021Article
- Glucose metabolism-related gene polymorphisms as the risk predictors of type 2 diabetes.Diabetology & metabolic syndrome · 2020Review
- Characterization of Exome Variants and Their Metabolic Impact in 6,716 American Indians from the Southwest US.American journal of human genetics · 2020Article
- Impact of a High Intake of Dairy Product on Insulin Sensitivity in Hyperinsulinemic Adults: A Crossover Randomized Controlled Trial.Current developments in nutrition · 2019Article
- Brain Glucose-Sensing Mechanism and Energy Homeostasis.Molecular neurobiology · 2019Review
- Impaired β-cell glucokinase as an underlying mechanism in diet-induced diabetes.Disease models & mechanisms · 2018Article
- Integrated analysis of the gene expression profile and DNA methylation profile of obese patients with type 2 diabetes.Molecular medicine reports · 2018Article
- Genome-wide association study for reproductive traits in a Large White pig population.Animal genetics · 2018Article
- Blood-Based DNA Methylation Biomarkers for Type 2 Diabetes: Potential for Clinical Applications.Frontiers in endocrinology · 2018Review
- Dairy Product Consumption Interacts with Glucokinase (GCK) Gene Polymorphisms Associated with Insulin Resistance.Journal of personalized medicine · 2017Article
- Exercise Metabolism in Nonobese Patients with Type 2 Diabetes Following the Acute Restoration of Normoglycaemia.Journal of diabetes research · 2017Article
- Association of gene coding variation and resting metabolic rate in a multi-ethnic sample of children and adults.BMC obesity · 2017Article
- The impact of genetic variants on BMI increase during childhood versus adulthood.International journal of obesity (2005) · 2016Article
- Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes.Endocrine reviews · 2016Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisGlucokinase (GCK) plays a role in glucose metabolism and glucose-stimulated insulin secretion. Rare mutations in GCK cause MODY. We investigated whether common variation (minor allele frequency ≥0.01) in GCK is associated with metabolic traits and type 2 diabetes.
methodsFour exonic single-nucleotide polymorphisms (SNPs) and three SNPs predicted to cause loss of promoter function were identified in whole-genome sequence data from 234 Pima Indians. These seven tag SNPs and rs4607517, a type 2 diabetes variant established in other studies, were analysed in 415 full-heritage non-diabetic Pima Indians characterised for metabolic traits, and 7,667 American Indians who had data on type 2 diabetes and BMI.
resultsA novel 3' untranslated region (3'UTR) SNP, chr7:44184184-G/A, was associated with the rate of carbohydrate oxidation post-absorptively (β = 0.22 mg [kg estimated metabolic body size (EMBS)](-1) min(-1), p = 0.005) and during a hyperinsulinaemic-euglycaemic clamp (β = 0.24 mg [kg EMBS](-1) min(-1), p = 0.0002), the rate of carbohydrate oxidation in a respiratory chamber (β = 311 kJ/day, p = 0.03) and 24 h energy expenditure, which was attributable to the thermic effect of food (β = 520 kJ/day, p = 3.39 × 10(-6)). This 3'UTR SNP was also associated with diabetes (OR 1.36, 95% CI 1.11, 1.65, p = 0.002), where the A allele (allele frequency 0.05) was associated with a lower rate of carbohydrate oxidation, lower 24 h energy expenditure and higher risk for diabetes. In a Cox proportional hazards model, a rate of insulin-stimulated carbohydrate oxidation lower than the mean rate at baseline predicted a higher risk for developing diabetes than for those above the mean (hazard rate ratio 2.2, 95% CI 1.3, 3.6, p = 0.002). CONCLUSIONS/
interpretationCommon variation in GCK influences the rate of carbohydrate oxidation, 24 h energy expenditure and diabetes risk in Pima Indians.
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