ArticleDiabetologia2009
Combined effects of single-nucleotide polymorphisms in GCK, GCKR, G6PC2 and MTNR1B on fasting plasma glucose and type 2 diabetes risk.
Article in Diabetologia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 6 of them syntheses that pooled it.
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Who cites it
38 citing papers in PubMed, 6 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Meta-analyses of the association of G6PC2 allele variants with elevated fasting glucose and type 2 diabetes.PloS one · 2017Pooled it
- Association of glucokinase regulatory protein polymorphism with type 2 diabetes and fasting plasma glucose: a meta-analysis.Molecular biology reports · 2013Pooled it
- Pooled it
- Genetic polymorphism of glucokinase on the risk of type 2 diabetes and impaired glucose regulation: evidence based on 298,468 subjects.PloS one · 2013Pooled it
- A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.PLoS genetics · 2012Pooled it
- Pooled it
- Trial
- Prevalence ofJournal of obesity · 2023Article
- Potential impact ofMolecular medicine reports · 2022Article
- Haplotypes of the genes (GCK and G6PC2) underlying the glucose/glucose-6-phosphate cycle are associated with pancreatic beta cell glucose sensitivity in patients with newly diagnosed type 2 diabetes from the VNDS study (VNDS 11).Journal of endocrinological investigation · 2021Article
- Glucose metabolism-related gene polymorphisms as the risk predictors of type 2 diabetes.Diabetology & metabolic syndrome · 2020Review
- Obesity genetics and cardiometabolic health: Potential for risk prediction.Diabetes, obesity & metabolism · 2019Review
- Association of Melatonin Pathway Gene's Single-Nucleotide Polymorphisms with Systemic Lupus Erythematosus in a Chinese Population.Journal of immunology research · 2019Article
- Exposure to Night-Time Traffic Noise, Melatonin-Regulating Gene Variants and Change in Glycemia in Adults.International journal of environmental research and public health · 2017Article
- Article
- Effects ofJournal of molecular endocrinology · 2017Article
- Susceptibility to type 2 diabetes may be modulated by haplotypes in G6PC2, a target of positive selection.BMC evolutionary biology · 2017Article
- Article
- A common variant in the MTNR1b gene is associated with increased risk of impaired fasting glucose (IFG) in youth with obesity.Obesity (Silver Spring, Md.) · 2015Article
- MTNR1B Genetic Variability Is Associated with Gestational Diabetes in Czech Women.International journal of endocrinology · 2014Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisVariation in fasting plasma glucose (FPG) within the normal range is a known risk factor for the development of type 2 diabetes. Several reports have shown that genetic variation in the genes for glucokinase (GCK), glucokinase regulatory protein (GCKR), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2) and melatonin receptor type 1B (MTNR1B) is associated with FPG. In this study we examined whether these loci also contribute to type 2 diabetes susceptibility.
methodsA random selection from the Dutch New Hoorn Study was used for replication of the association with FGP (2,361 non-diabetic participants). For the genetic association study we extended the study sample with 2,628 participants with type 2 diabetes. Risk allele counting was used to calculate a four-gene risk allele score for each individual.
resultsVariants of the GCK, G6PC2 and MTNR1B genes but not GCKR were associated with FPG (all, p <or= 0.001; GCKR, p = 0.23). Combining these four genes in a risk allele score resulted in an increase of 0.05 mmol/l (0.04-0.07) per additional risk allele (p = 2 x 10(-13)). Furthermore, participants with less than three or more than five risk alleles showed significantly different type 2 diabetes susceptibility compared with the most common group with four risk alleles (OR 0.77 [0.65-0.93], p = 0.005 and OR 2.05 [1.50-2.80], p = 4 x 10(-6) respectively). The age at diagnosis was also significantly associated with the number of risk alleles (p = 0.009).
conclusionsA combined risk allele score for single-nucleotide polymorphisms in four known FPG loci is significantly associated with FPG and HbA(1c) in a Dutch population-based sample of non-diabetic participants. Carriers of low or high numbers of risk alleles show significantly different risks for type 2 diabetes compared with the reference group.
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