ArticleDiabetologia2003
T130I mutation in HNF-4alpha gene is a loss-of-function mutation in hepatocytes and is associated with late-onset Type 2 diabetes mellitus in Japanese subjects.
Article in Diabetologia, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genome-wide association meta-analysis yields 20 loci associated with gallstone disease.Nature communications · 2018Pooled it
- Pharmacogenetic effects of regulatory nuclear receptors (PXR, CAR, RXRα and HNF4α) on docetaxel disposition in Chinese nasopharyngeal cancer patients.European journal of clinical pharmacology · 2014Trial
- PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients.The pharmacogenomics journal · 2008Trial
- HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes.Nature communications · 2024Article
- Functional characterization of HNF4A gene variants identify promoter and cell line specific transactivation effects.Human molecular genetics · 2024Article
- Functional Analysis of a NovelJournal of the Endocrine Society · 2024Article
- The roles of nuclear receptors in cholesterol metabolism and reverse cholesterol transport in nonalcoholic fatty liver disease.Hepatology communications · 2024Review
- Repurposing Doxepin to Ameliorate Steatosis and Hyperglycemia by Activating FAM3A Signaling Pathway.Diabetes · 2020Article
- Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.Nature genetics · 2019Article
- Maturity-onset diabetes of the young as a model for elucidating the multifactorial origin of type 2 diabetes mellitus.Journal of diabetes investigation · 2018Review
- Susceptibility background for type 2 diabetes in eleven Mexican Indigenous populations: HNF4A gene analysis.Molecular genetics and genomics : MGG · 2017Article
- Crosstalk of HNF4Acta pharmaceutica Sinica. B · 2016Review
- Understanding the Importance of Gene and Environment in the Etiology and Prevention of Type 2 Diabetes Mellitus in High-Risk Populations.Oral health case reports · 2016Article
- Assessment of established HDL-C loci for association with HDL-C levels and type 2 diabetes in Pima Indians.Diabetologia · 2016Article
- Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes.Journal of diabetes research · 2016Article
- Genetics of type 2 diabetes.World journal of diabetes · 2013Article
- What will diabetes genomes tell us?Current diabetes reports · 2012Review
- A role for coding functional variants in HNF4A in type 2 diabetes susceptibility.Diabetologia · 2011Article
- Genetic causes of high and low serum HDL-cholesterol.Journal of lipid research · 2010Review
- Developmental and tissue-specific regulation of hepatocyte nuclear factor 4-alpha (HNF4-alpha) isoforms in rodents.Gene expression · 2010Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisMutations in hepatocyte nuclear factor (HNF)-4alpha gene cause a form of maturity-onset diabetes of the young (MODY1). The T130I mutation is a rare missense mutation, which affects a conserved amino acid in a DNA binding domain. This mutation can be found in the general population, so this variant alone does not cause MODY. However, its significance in the development of late-onset Type 2 diabetes is not known.
methodsWe screened 423 unrelated Japanese patients with late-onset Type 2 diabetes and 354 unrelated non-diabetic control subjects for the T130I mutation in the HNF-4alpha gene. The transactivation ability of T130I-HNF-4alpha was assessed using reporter gene assay.
resultsThe frequency of the T130I mutation was higher in Type 2 diabetic patients ( p=0.015, odds ratio 4.3, 95%CI 1.24-14.98) than control subjects. The serum HDL-cholesterol concentration was lower in Type 2 diabetic patients with the T130I mutation compared with those without this mutation ( p=0.006). Reporter gene analysis showed that T130I-HNF-4alpha transcriptional activity was not impaired compared with wild-type HNF-4alpha in Hela and MIN6 cells, but it was reduced in HepG2 and primary cultured mouse hepatocytes (27-78% of wild type, p<0.05). CONCLUSION/
interpretationOur findings suggest that T130I-HNF-4alpha is a loss-of-function mutation in hepatocytes and that this mutation is associated with late-onset Type 2 diabetes in Japanese subjects. The T130I mutation in the HNF-4alpha gene might be involved in the development of Type 2 diabetes in the Japanese population.
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