ArticleDiabetologia2005
Association of childhood type 1 diabetes mellitus with a variant of PAX4: possible link to beta cell regenerative capacity.
Article in Diabetologia, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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32 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci.PLoS genetics · 2011Pooled it
- Association of PAX4 genetic variants with oral antidiabetic drugs efficacy in Chinese type 2 diabetes patients.The pharmacogenomics journal · 2014Trial
- Polygenic score from MODY genes is associated with type 1 diabetes and disease characteristics.Acta diabetologica · 2025Article
- RareBiomedicines · 2025Article
- In Silico Functional and Structural Analysis of Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in Human Paired Box 4 Gene.Biochemical genetics · 2024Article
- Maturity-onset diabetes of the young type 9 or latent autoimmune diabetes in adults: A case report and review of literature.World journal of diabetes · 2023Article
- Pax4 in Health and Diabetes.International journal of molecular sciences · 2023Review
- Novel approaches to the treatment of type 1 diabetes.Journal of diabetes · 2022Article
- Input-output signal processing plasticity of vagal motor neurons in response to cardiac ischemic injury.iScience · 2021Article
- Genetics and Pathophysiology of Maturity-onset Diabetes of the Young (MODY): A Review of Current Trends.Oman medical journal · 2020Review
- Identification of the First PAX4-MODY Family Reported in Brazil.Diabetes, metabolic syndrome and obesity : targets and therapy · 2020Article
- Micro-ribonucleic acid-binding site variants of type 2 diabetes candidate loci predispose to gestational diabetes mellitus in Chinese Han women.Journal of diabetes investigation · 2018Article
- Generation and Phenotype Identification ofG3 (Bethesda, Md.) · 2018Article
- The rs10229583 polymorphism near paired box gene 4 is associated with gestational diabetes mellitus in Chinese women.The Journal of international medical research · 2018Article
- Genetic Testing of Maturity-Onset Diabetes of the Young Current Status and Future Perspectives.Frontiers in endocrinology · 2018Review
- PAX4 R192H and P321H polymorphisms in type 2 diabetes and their functional defects.Journal of human genetics · 2016Article
- Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes.Endocrine reviews · 2016Review
- Transcriptional control of PAX4-regulated miR-144/451 modulates metastasis by suppressing ADAMs expression.Oncogene · 2015Article
- Simulated microgravity combined with polyglycolic acid scaffold culture conditions improves the function of pancreatic islets.BioMed research international · 2013Article
- No association of the IRS1 and PAX4 genes with type I diabetes.Genes and immunity · 2009Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisLoss of pancreatic beta cells is the crucial event in the development of type 1 diabetes. It is the result of an imbalance between autoimmune destruction and insufficient regeneration of islet cells. To study the role of islet cell regeneration in the pathogenesis of type 1 diabetes, we focused on PAX4, a paired homeodomain transcriptional repressor that is involved in islet cell growth.
methodsThe study included 379 diabetic children and 1,070 controls from two distinct populations, and a cohort of children who had not developed type 1 diabetes, despite the presence of islet cell antibodies. Genomic DNA analysis of PAX4 was carried out via direct sequencing of PCR-amplified fragments and allelic discrimination. We compared the transrepression potential of the PAX4 variants in betaTC3 cells and analysed their influence on beta cell growth.
resultsThe type 1 diabetic subjects are different from the normal individuals in terms of the genotype distribution of the A1168C single nucleotide polymorphism in PAX4. The C/C genotype is frequent among type 1 diabetic children (73%) and rare among the control population (32%). Conversely, the A/C genotype is prevalent among control subjects (62%) and antibody-positive children without type 1 diabetes (73.6%), but uncommon among subjects with type 1 diabetes (17.5%). The combination of PAX4A and PAX4C is functionally more active than PAX4C alone (the "diabetic" variant). Beta cells expressing PAX4A and PAX4C efficiently proliferate when stimulated with glucose, whereas cells expressing the PAX4C variant alone do not. CONCLUSIONS/
interpretationWe have identified a link between beta cell regenerative capacity and susceptibility to type 1 diabetes. This finding could explain the fact that not all of the individuals who develop autoimmunity against beta cells actually contract the disease. The C/C genotype of the A1168C polymorphism in PAX4 can be viewed as a predisposition marker that can help to detect individuals prone to develop type 1 diabetes.
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