caa a22 4500 475772512 CHVBK 20180406123621.0 cr unu---uuuuu 170329e20000801xx s 000 0 eng 10.1007/s001250051491 doi (NATIONALLICENCE)springer-10.1007/s001250051491 No diabetes-associated mutations in the coding region of the hepatocyte nuclear factor-4γ gene (HNF4G) in Japanese patients with MODY [Elektronische Daten] [M. Hara, X. Wang, V. P. Paz, N. J. Cox, N. Iwasaki, M. Ogata, Y. Iwamoto, G. I. Bell] Aims/hypothesis. Mutations in the transcription factor hepatocyte nuclear factor (HNF)-4α are the cause of one form of maturity-onset diabetes of the young, MODY1. The HNF-4γ is structurally related to HNF-4α and is expressed together with HNF-4α in pancreatic islets. We therefore tested the hypothesis that genetic variation in the HNF-4γ 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-4γ 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. [Diabetologia (2000) 43: 1064-1069] Springer-Verlag Berlin Heidelberg, 2000 Keywords Maturity-onset diabetes of the young nationallicence MODY nationallicence transcription factor nationallicence nuclear receptor nationallicence HNF-4γ nationallicence diabetes mellitus nationallicence insulin nationallicence genetics nationallicence mutation nationallicence Hara M. Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA, US aut Wang X. Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA, US aut Paz V. P. Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA, US aut Cox N. J. Departments of Human Genetics and Medicine, The University of Chicago, Chicago, Illinois, USA, US aut Iwasaki N. Diabetes Centre, Tokyo Women's Medical University, Tokyo, Japan, JP aut Ogata M. Diabetes Centre, Tokyo Women's Medical University, Tokyo, Japan, JP aut Iwamoto Y. Diabetes Centre, Tokyo Women's Medical University, Tokyo, Japan, JP aut Bell G. I. Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA, US aut https://doi.org/10.1007/s001250051491 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051491 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hara M. Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA, US aut NATIONALLICENCE 700 1- Wang X. Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA, US aut NATIONALLICENCE 700 1- Paz V. P. Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA, US aut NATIONALLICENCE 700 1- Cox N. J. Departments of Human Genetics and Medicine, The University of Chicago, Chicago, Illinois, USA, US aut NATIONALLICENCE 700 1- Iwasaki N. Diabetes Centre, Tokyo Women's Medical University, Tokyo, Japan, JP aut NATIONALLICENCE 700 1- Ogata M. Diabetes Centre, Tokyo Women's Medical University, Tokyo, Japan, JP aut NATIONALLICENCE 700 1- Iwamoto Y. Diabetes Centre, Tokyo Women's Medical University, Tokyo, Japan, JP aut NATIONALLICENCE 700 1- Bell G. I. Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer