SynthesisDiabetologia2010
Variants at DGKB/TMEM195, ADRA2A, GLIS3 and C2CD4B loci are associated with reduced glucose-stimulated beta cell function in middle-aged Danish people.
Synthesis in Diabetologia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 5 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
66 citing papers in PubMed, 5 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- Pooled it
- Meta-analysis of genome-wide association study of homeostasis model assessment β cell function and insulin resistance in an East Asian population and the European results.Molecular genetics and genomics : MGG · 2014Pooled it
- Systematic evaluation of validated type 2 diabetes and glycaemic trait loci for association with insulin clearance.Diabetologia · 2013Pooled it
- Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets.PLoS genetics · 2013Pooled it
- Variants of ADRA2A are associated with fasting glucose, blood pressure, body mass index and type 2 diabetes risk: meta-analysis of four prospective studies.Diabetologia · 2011Pooled it
- Genetic variation at glucose and insulin trait loci and response to glucose-insulin-potassium (GIK) therapy: the IMMEDIATE trial.The pharmacogenomics journal · 2015Trial
- The diabetogenic VPS13C/C2CD4A/C2CD4B rs7172432 variant impairs glucose-stimulated insulin response in 5,722 non-diabetic Danish individuals.Diabetologia · 2011Trial
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- Influence of Fatty Acid Desaturase Enzyme-1 Gene (FADS-1) Polymorphism on Serum Polyunsaturated Fatty Acids Levels, Desaturase Enzymes, Lipid Profile, and Glycemic Control Parameters in Newly Diagnosed Diabetic Mellitus Patients.International journal of molecular sciences · 2025Article
- Discovery of host genetic factors through multi-locus GWAS against toxoplasmosis in sheep: addressing one health perspectives.BMC veterinary research · 2025Article
- Parent-of-origin effects of phosphatidyl inositol-bisphosphate hydrolysis pathway genes on type 2 diabetes and the modification effect by obesity.Frontiers in endocrinology · 2025Article
- Article
- DINGO: increasing the power of locus discovery in maternal and fetal genome-wide association studies of perinatal traits.Nature communications · 2024Article
- Genetic architecture of oral glucose-stimulated insulin release provides biological insights into type 2 diabetes aetiology.Nature metabolism · 2024Article
- C2CD4B Evokes Oxidative Stress and Vascular Dysfunction via a PI3K/Akt/PKCα-Signaling Pathway.Antioxidants (Basel, Switzerland) · 2024Article
- Association between the MTNR1B, HHEX, SLC30A8, and TCF7L2 single nucleotide polymorphisms and cardiometabolic risk profile in a mixed ancestry South African population.Scientific reports · 2023Article
- The Association betweenGenes · 2023Article
- AGMO Inhibitor Reduces 3T3-L1 Adipogenesis.Cells · 2021Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisA meta-analysis of 21 genome-wide association studies identified 11 novel genetic loci implicated in fasting glucose homeostasis. We aimed to evaluate the impact of these variants on insulin release and insulin sensitivity estimated from OGTTs.
methodsEleven variants in or near DGKB/TMEM195, ADCY5, MADD, ADRA2A, FADS1, CRY2, SLC2A2, GLIS3, PROX1, C2CD4B and IGF1 were genotyped in 6,784 middle-aged participants of the population-based Inter99 cohort. Association studies of quantitative estimates of insulin release and insulin sensitivity were performed in 5,722 non-diabetic Danish participants on whom an OGTT was performed.
resultsAssuming an additive genetic model, carriers of the alleles increasing fasting glucose in DGKB/TMEM195, ADRA2A, GLIS3 and C2CD4B showed decreased glucose-stimulated insulin release as assessed by the BIGTT-acute insulin response index (2.7-3.5%; p < 0.005 for all) and by corrected insulin response (2.8-5.9%; p < 0.03 for all). In addition, the PROX1 glucose-raising allele showed a 2.9% decreased corrected insulin response (p = 0.03), while the hyperglycaemic allele of variants in or near ADRA2A, FADS1, CRY2 and C2CD4B were associated with a 2.6% to 9.3% decrease in one or both of two different OGTT-based disposition indices (p < 0.02 for all). After correction for multiple testing, variants in the DGKB/TMEM195, ADRA2A, GLIS3 and C2CD4B loci were associated with estimates of beta cell function. CONCLUSIONS/
interpretationWe found that the lead variants at the DGKB/TMEM195, ADRA2A, GLIS3 and C2CD4B loci were associated with decreased glucose-stimulated insulin response. This association underlines the importance of pancreatic beta cell dysfunction in the genetic predisposition to hyperglycaemia and type 2 diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.