ArticleDiabetes2010
Genetic and functional assessment of the role of the rs13431652-A and rs573225-A alleles in the G6PC2 promoter that are strongly associated with elevated fasting glucose levels.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.
- Meta-analyses of the association of G6PC2 allele variants with elevated fasting glucose and type 2 diabetes.PloS one · 2017Pooled it
- Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource.Diabetologia · 2012Pooled it
- G6PC2 controls glucagon secretion by defining the set point for glucose in pancreatic α cells.Science translational medicine · 2025Article
- Identification of structural motifs critical for human G6PC2 function informed by sequence analysis and an AlphaFold2-predicted model.Bioscience reports · 2024Article
- Article
- G6PC1 and G6PC2 influence G6P flux but not HSD11B1 activity.Journal of molecular endocrinology · 2023Article
- Stem Cell-Derived β Cells: A Versatile Research Platform to Interrogate the Genetic Basis of β Cell Dysfunction.International journal of molecular sciences · 2022Review
- Effects of Genetic Variants of Nuclear Receptor Y on the Risk of Type 2 Diabetes Mellitus.Journal of diabetes research · 2019Article
- Identification and functional analysis of glycemic trait loci in the China Health and Nutrition Survey.PLoS genetics · 2018Article
- Effects ofJournal of molecular endocrinology · 2017Article
- G6PC2 Modulates the Effects of Dexamethasone on Fasting Blood Glucose and Glucose Tolerance.Endocrinology · 2016Article
- G6PC2 Modulates Fasting Blood Glucose In Male Mice in Response to Stress.Endocrinology · 2016Article
- USAT: A Unified Score-Based Association Test for Multiple Phenotype-Genotype Analysis.Genetic epidemiology · 2016Article
- Article
- Novel stable isotope analyses demonstrate significant rates of glucose cycling in mouse pancreatic islets.Diabetes · 2015Article
- 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
- Moving on from GWAS: functional studies on the G6PC2 gene implicated in the regulation of fasting blood glucose.Current diabetes reports · 2013Article
- Multiple functional polymorphisms in the G6PC2 gene contribute to the association with higher fasting plasma glucose levels.Diabetologia · 2013Article
- Article
- From genetic association to molecular mechanism.Current diabetes reports · 2010Review
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Authors and funding
23 authors at 12 institutions in 5 countries.
Funding
Abstract
objectiveGenome-wide association studies have identified a single nucleotide polymorphism (SNP), rs560887, located in a G6PC2 intron that is highly correlated with variations in fasting plasma glucose (FPG). G6PC2 encodes an islet-specific glucose-6-phosphatase catalytic subunit. This study examines the contribution of two G6PC2 promoter SNPs, rs13431652 and rs573225, to the association signal. RESEARCH DESIGN AND
methodsWe genotyped 9,532 normal FPG participants (FPG <6.1 mmol/l) for three G6PC2 SNPs, rs13431652 (distal promoter), rs573225 (proximal promoter), rs560887 (3rd intron). We used regression analyses adjusted for age, sex, and BMI to assess the association with FPG and haplotype analyses to assess comparative SNP contributions. Fusion gene and gel retardation analyses characterized the effect of rs13431652 and rs573225 on G6PC2 promoter activity and transcription factor binding.
resultsGenetic analyses provide evidence for a strong contribution of the promoter SNPs to FPG variability at the G6PC2 locus (rs13431652: β = 0.075, P = 3.6 × 10(-35); rs573225 β = 0.073 P = 3.6 × 10(-34)), in addition to rs560887 (β = 0.071, P = 1.2 × 10(-31)). The rs13431652-A and rs573225-A alleles promote increased NF-Y and Foxa2 binding, respectively. The rs13431652-A allele is associated with increased FPG and elevated promoter activity, consistent with the function of G6PC2 in pancreatic islets. In contrast, the rs573225-A allele is associated with elevated FPG but reduced promoter activity.
conclusionsGenetic and in situ functional data support a potential role for rs13431652, but not rs573225, as a causative SNP linking G6PC2 to variations in FPG, though a causative role for rs573225 in vivo cannot be ruled out.
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