Genetic analysis revealed a novel variant (p.Pro190Leu) in HNF4A, which is located in the ligand binding domain of the transcription factor, and the p.Glu23Lys variant in KCNJ11, which is associated with type 2 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.
The four polymorphisms, rs4810424, rs1884613, rs1884614 and rs2144908, in the HNF‑4α gene were not the susceptible loci for type 2 diabetes in the Bai population of Dali city, however, the haplotype, CCTA, built from the four SNPs may increase the risk of type 2 diabetes in this population.
All 13 known MODY genes, genes identified from a genome-wide linkage study or genome-wide association studies as increasing the risk of type 2 diabetes and genes causing diabetes in animal models, were included in the custom panel.
Our findings functionally link the miR-24/MODY gene regulatory pathway to the onset of type 2 diabetes and create a novel network between nutrient overload and genetic diabetes via miR-24.
This study considers the phenotypes that result from glucokinase defects and the relationship of MODY to NIDDM, and it estimates the role of glucokinase defects in NIDDM in general.
A genome-wide association study reported FITM2-R3H domain containing like-HNF4A locus to be associated with type 2 diabetes (T2DM) in East Asian populations.
Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor-1alpha genes in patients with early-onset type 2 diabetes mellitus/MODY.
The purpose of this study was to determine whether alterations in known MODY genes and two MODY candidate genes contribute to the development of early-onset type 2 diabetes in Pima Indians.
Concerning the Gly15Gly polymorphism, the TT genotype was found in 275 subjects (79.9%), the TG genotype in 67 subjects (19.5%) and the GG genotype in 2 subjects (0.6%): one with maturity onset diabetes of young age (MODY-diabetes) and one with Lipoatrophic Diabetes Syndrome (LPDS).
Genetic association studies have provided evidence for a common genetic background (upstream transcription factor 1, activating transcription factor 6, transcription factor 7-like 2 and hepatocyte nuclear factor 4 alpha) between FCHL and T2DM.
Mutations in an unknown locus (MODY1) on chromosome 20 and the glucokinase gene (MODY2) on chromosome 7 can cause this form of non-insulin-dependent diabetes.
A hepatocyte nuclear factor-4 alpha gene (HNF4A) P2 promoter haplotype linked with late-onset diabetes: studies of HNF4A variants in the Norwegian MODY registry.
Seven mutations in the hepatocyte nuclear factor (HNF)-4alpha gene have been shown to correlate with type 1 maturity-onset diabetes of the young (MODY 1), a monogenic form of type 2 diabetes.
Mutations in the hepatocyte nuclear factor (HNF)-1alpha and glucokinase (GCK) genes are the major causes of monogenic forms of Type II (non-insulin-dependent) diabetes mellitus (Maturity-Onset Diabetes of the Young subtypes, MODY).