ArticleDiabetes2009
A single-nucleotide polymorphism in a methylatable Foxa2 binding site of the G6PC2 promoter is associated with insulin secretion in vivo and increased promoter activity in vitro.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Meta-analyses of the association of G6PC2 allele variants with elevated fasting glucose and type 2 diabetes.PloS one · 2017Pooled it
- The unanticipated role of the glial-associated glucose-6-phosphatase system in brain homeostasis.iScience · 2025Review
- G6PC2 controls glucagon secretion by defining the set point for glucose in pancreatic α cells.Science translational medicine · 2025Article
- Association ofGlobal medical genetics · 2023Article
- A genome-wide analysis of DNA methylation identifies a novel association signal for Lp(a) concentrations in the LPA promoter.PloS one · 2020Article
- 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
- Mapping I-A(g7) restricted epitopes in murine G6PC2.Immunologic research · 2013Article
- Contribution of transcription factor binding site motif variants to condition-specific gene expression patterns in budding yeast.PloS one · 2012Article
- From genetic association to molecular mechanism.Current diabetes reports · 2010Review
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Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe G6PC2 gene encoding islet-specific glucose-6-phosphatase related protein (IGRP) has a common promoter variant, rs573225 (-231G/A), located within a Foxa binding site. We tested the cis-regulatory effects of rs573225 on promoter activity and its association with insulin response to oral glucose. RESEARCH DESIGN AND
methodsFunctional effects of rs573225 were explored in transfected INS-1 and HIT-T beta-cell lines. A total of 734 young obese subjects of European ancestry were genotyped for rs573225. Insulin and glucose levels were measured in response to oral glucose, and the insulinogenic index (IGI) of insulin secretion was calculated.
resultsIn vitro, the G allele showed a higher affinity for binding Foxa2 transcription factor and increased G6PC2 promoter activity. Foxa2 binding is modified if the C adjacent to the G allele is methylated. IGI was associated with rs573225 by linear regression analysis and was 30% greater in AA or AG than in GG obese children. rs573225 was also associated with fasting glucose.
conclusionsrs573225 is a functional cis-regulatory (epi)-single-nucleotide polymorphism (SNP) of G6PC2 associated with glucose-insulin homeostasis in obese children, likely to explain the results of recent genome-wide association studies in nondiabetic adults.
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