ArticleDiabetologia2011
A role for coding functional variants in HNF4A in type 2 diabetes susceptibility.
Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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15 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Prediabetes is associated with HNF-4 α P2 promoter polymorphism rs1884613: a case-control study in Han Chinese population and an updated meta-analysis.Disease markers · 2014Pooled it
- Transcription factor HNF4α2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophy.The Journal of clinical investigation · 2023Article
- Gain of Function of Malate Dehydrogenase 2 and Familial Hyperglycemia.The Journal of clinical endocrinology and metabolism · 2022Observational
- Maturity Onset Diabetes of the Young-New Approaches for Disease Modelling.International journal of molecular sciences · 2021Review
- Type 2 Diabetes-Associated Genetic Polymorphisms as Potential Disease Predictors.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Review
- Susceptibility background for type 2 diabetes in eleven Mexican Indigenous populations: HNF4A gene analysis.Molecular genetics and genomics : MGG · 2017Article
- The Common p.R114W HNF4A Mutation Causes a Distinct Clinical Subtype of Monogenic Diabetes.Diabetes · 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
- Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.Nature genetics · 2015Article
- Candidate gene association study of coronary artery calcification in chronic kidney disease: findings from the CRIC study (Chronic Renal Insufficiency Cohort).Journal of the American College of Cardiology · 2013Article
- What will diabetes genomes tell us?Current diabetes reports · 2012Review
- Examination of Rare Variants in HNF4 α in European Americans with Type 2 Diabetes.Journal of diabetes & metabolism · 2011Article
- MODY: history, genetics, pathophysiology, and clinical decision making.Diabetes care · 2011Review
- Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment.Genes and immunityArticle
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Authors and funding
25 authors at 15 institutions in 4 countries.
Funding
Abstract
aims/hypothesisRare mutations in the gene HNF4A, encoding the transcription factor hepatocyte nuclear factor 4α (HNF-4A), account for ~5% of cases of MODY and more frequent variants in this gene may be involved in multifactorial forms of diabetes. Two low-frequency, non-synonymous variants in HNF4A (V255M, minor allele frequency [MAF] ~0.1%; T130I, MAF ~3.0%)-known to influence downstream HNF-4A target gene expression-are of interest, but previous type 2 diabetes association reports were inconclusive. We aimed to evaluate the contribution of these variants to type 2 diabetes susceptibility through large-scale association analysis.
methodsWe genotyped both variants in at least 5,745 cases and 14,756 population controls from the UK and Denmark. We also undertook an expanded association analysis that included previously reported and novel genotype data obtained in Danish, Finnish, Canadian and Swedish samples. A meta-analysis incorporating all published association studies of the T130I variant was subsequently carried out in a maximum sample size of 14,279 cases and 26,835 controls.
resultsWe found no association between V255M and type 2 diabetes in either the initial (p = 0.28) or the expanded analysis (p = 0.44). However, T130I demonstrated a modest association with type 2 diabetes in the UK and Danish samples (additive per allele OR 1.17 [95% CI 1.08-1.28]; p = 1.5 × 10⁻⁴), which was strengthened in the meta-analysis (OR 1.20 [95% CI 1.10-1.30]; p = 2.1 × 10⁻⁵). CONCLUSIONS/
interpretationOur data are consistent with T130I as a low-frequency variant influencing type 2 diabetes risk, but are not conclusive when judged against stringent standards for genome-wide significance. This study exemplifies the difficulties encountered in association testing of low-frequency variants.
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