Trial reportDiabetologia2011
The diabetogenic VPS13C/C2CD4A/C2CD4B rs7172432 variant impairs glucose-stimulated insulin response in 5,722 non-diabetic Danish individuals.
Trial report in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity.Diabetes · 2014Pooled it
- Genetic variation at glucose and insulin trait loci and response to glucose-insulin-potassium (GIK) therapy: the IMMEDIATE trial.The pharmacogenomics journal · 2015Trial
- A Pilot Study on the Proteomics Profile of Serum Exosome-Enriched Extracellular Vesicles from Normal versus Individuals with Obesity-Related Insulin Resistance.Biomedicines · 2024Article
- C2CD4B Evokes Oxidative Stress and Vascular Dysfunction via a PI3K/Akt/PKCα-Signaling Pathway.Antioxidants (Basel, Switzerland) · 2024Article
- Reflections on the state of diabetes research and prospects for treatment.Diabetology international · 2023Review
- Yeast as a Model to Find New Drugs and Drug Targets forInternational journal of molecular sciences · 2022Review
- Sexually dimorphic roles for the type 2 diabetes-associated C2cd4b gene in murine glucose homeostasis.Diabetologia · 2021Article
- TBC1D1 interacting proteins, VPS13A and VPS13C, regulate GLUT4 homeostasis in C2C12 myotubes.Scientific reports · 2020Article
- Functional Genomics in Pancreatic β Cells: Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.Frontiers in endocrinology · 2020Review
- Identification ofProceedings of the National Academy of Sciences of the United States of America · 2019Article
- VPS13A is closely associated with mitochondria and is required for efficient lysosomal degradation.Disease models & mechanisms · 2019Article
- Yeast-model-based study identified myosin- and calcium-dependent calmodulin signalling as a potential target for drug intervention in chorea-acanthocytosis.Disease models & mechanisms · 2019Article
- Silencing of the FTO gene inhibits insulin secretion: An in vitro study using GRINCH cells.Molecular and cellular endocrinology · 2018Article
- A Common Type 2 Diabetes Risk Variant Potentiates Activity of an Evolutionarily Conserved Islet Stretch Enhancer and Increases C2CD4A and C2CD4B Expression.American journal of human genetics · 2018Article
- Principles and methods of in-silico prioritization of non-coding regulatory variants.Human genetics · 2018Review
- Vacuolar protein sorting 13C is a novel lipid droplet protein that inhibits lipolysis in brown adipocytes.Molecular metabolism · 2018Article
- Changes in the expression of the type 2 diabetes-associated gene VPS13C in the β-cell are associated with glucose intolerance in humans and mice.American journal of physiology. Endocrinology and metabolism · 2016Article
- USAT: A Unified Score-Based Association Test for Multiple Phenotype-Genotype Analysis.Genetic epidemiology · 2016Article
- Identification of VPS13C as a Galectin-12-Binding Protein That Regulates Galectin-12 Protein Stability and Adipogenesis.PloS one · 2016Article
- Potential of pluripotent stem cells for diabetes therapy.Current diabetes reports · 2012Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisA genome-wide association study in the Japanese population reported two genome-wide significant loci associated with type 2 diabetes of which the VPS13C/C2CD4A/C2CD4B locus was replicated in Europeans. We looked for potential associations between the diabetogenic VPS13C/C2CD4A/C2CD4B rs7172432 variant and diabetes-related intermediary traits.
methodsWe genotyped the rs7172432 variant in the population-based Inter99 cohort (n = 6,784) and analysed quantitative diabetes-related traits in 5,722 non-diabetic participants who all were examined by an OGTT.
resultsThe diabetes-associated A allele was associated with 0.60 cm higher waist circumference (p = 0.004), 0.037 mmol/l higher fasting plasma glucose (p = 4 × 10(-5)) and 0.11 mmol/l higher plasma glucose at 30 min during an OGTT (p = 4 × 10(-4)). In analyses adjusted for concomitant insulin sensitivity levels the diabetogenic allele was associated with a lower acute glucose-stimulated insulin response (GSIR) as estimated by 30 min serum insulin (β = -0.039, p = 2 × 10(-7)), insulinogenic index (β = -0.057, p = 1 × 10(-8)) and BIGTT-acute insulin release (β = -0.041, p = 9 × 10(-9)). As rs7172432 is situated in a region previously associated with glycaemic traits, we tested linkage disequilibrium (LD) with the reported regional lead single-nucleotide polymorphisms for fasting (rs11071657) and 2 h plasma glucose (rs17271305), and performed conditional analyses of rs7172432. Rs7172432 showed moderate LD with rs11071657 and rs17271305 (R (2) < 0.34) and we found strong association by almost unchanged effect sizes of rs7172432 with plasma glucose and estimates of GSIR in analyses conditional on rs11071657 and rs17271305. CONCLUSIONS/
interpretationThe diabetogenic VPS13C/C2CD4A/C2CD4B rs7172432 A allele associates with GSIR in non-diabetic individuals from the general population, suggesting an impaired beta cell function as an intermediary diabetes-related trait.
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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.