AIMS/HYPOTHESIS - Mutations in the transcription factor hepatocyte nuclear factor (HNF)-4alpha are the cause of one form of maturity-onset diabetes of the young, MODY1. The HNF-4gamma is structurally related to HNF-4alpha and is expressed together with HNF-4alpha in pancreatic islets. We therefore tested the hypothesis that genetic variation in the HNF-4gamma gene (HNF4G) is associated with MODY in Japanese subjects.
METHODS - We screened the protein coding region of HNF4G (exons 3-11) for mutations in 57 unrelated Japanese subjects with MODY by amplifying each exon and adjacent intron region using the polymerase chain reaction (PCR) and specific primers and then directly sequencing the PCR products. The frequency of each variant was compared between patients with MODY and a group of non-diabetic subjects.
RESULTS - We found ten sequence variants, two of these were located in exons: exon 6, a silent substitution in codon 144, c.432A/G and exon 7, a G-to-A substitution in codon 190 (c.570G/A) resulting in a conservative Met-to-Ile substitution (M/I190) in the putative ligand-binding region of HNF-4gamma protein. The remaining eight variants were located in introns. There was no significant difference in the frequency of these polymorphisms between subjects with MODY and non-diabetic control subjects.
CONCLUSION/INTERPRETATION - Genetic variation in the coding region of HNF4G is unlikely to be a major cause of MODY in Japanese people.