caa a22 4500 475771400 CHVBK 20180406123618.0 cr unu---uuuuu 170329e20000901xx s 000 0 eng 10.1007/s001250051512 doi (NATIONALLICENCE)springer-10.1007/s001250051512 Identification of missense mutations in the hepatocyte nuclear factor-3β gene in Japanese subjects with late-onset Type II diabetes mellitus [Elektronische Daten] [Q. Zhu, K. Yamagata, L. Yu, H. Tomura, S. Yamada, Q. Yang, I. Yoshiuchi, S. Sumi, J. Miyagawa, J. Takeda, T. Hanafusa, Y. Matsuzawa] Aims/hypothesis. Hepatocyte nuclear factor (HNF)-3β, a transcription factor expressed in pancreatic beta cells, is an upstream regulator of HNF-1α/MODY3, HNF-4α/MODY1 and IPF1/MODY5 genes. Our previous screening of MODY subjects showed that mutations in the HNF-3 β gene are not a common cause of this form of diabetes in the Japanese. We tested the hypothesis that mutations in the HNF-3 β gene cause late-onset Type II (non-insulin-dependent) diabetes mellitus in this population. Methods. Genotyping of the polymorphic TCC repeat in the HNF-3 β gene was done in 112 Japanese subjects with Type II diabetes (age at diagnosis > 35 and family history of Type II diabetes among their second-degree relatives) and 96 Japanese control subjects. Furthermore, we screened 57 Type II diabetic patients for mutations of the HNF-3 β gene. Transactivation activity of variant HNF-3β was investigated by transfection assay. Results. The distribution of alleles of the TCC repeat was similar between diabetic and control groups. Mutation screening identified two missense mutations, A86T and G114E. Neither mutation was observed in 225 control subjects. The transactivation activity of G114E-HNF-3β was similar to that of wild type-HNF-3β. In contrast, the activity of A86T-HNF-3β was statistically significantly reduced to 83-86 % of that of wild type. Conclusions/Interpretation. The A86T mutation in the HNF-3 β gene might be involved in the development of late-onset Type II diabetes in a small group of Japanese people. [Diabetologia (2000) 43: 1197-1200] Springer-Verlag Berlin Heidelberg, 2000 Keywords Keywords. HNF-3β nationallicence HNF-1α nationallicence mutation nationallicence genetics nationallicence Zhu Q. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut Yamagata K. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut Yu L. Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan, JP aut Tomura H. The Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan, JP aut Yamada S. The Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan, JP aut Yang Q. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut Yoshiuchi I. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut Sumi S. Suita Municipal Hospital, Suita, Osaka, Japan, JP aut Miyagawa J. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut Takeda J. The Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan, JP aut Hanafusa T. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut Matsuzawa Y. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut https://doi.org/10.1007/s001250051512 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051512 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhu Q. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut NATIONALLICENCE 700 1- Yamagata K. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut NATIONALLICENCE 700 1- Yu L. Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan, JP aut NATIONALLICENCE 700 1- Tomura H. The Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan, JP aut NATIONALLICENCE 700 1- Yamada S. The Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan, JP aut NATIONALLICENCE 700 1- Yang Q. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut NATIONALLICENCE 700 1- Yoshiuchi I. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut NATIONALLICENCE 700 1- Sumi S. Suita Municipal Hospital, Suita, Osaka, Japan, JP aut NATIONALLICENCE 700 1- Miyagawa J. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut NATIONALLICENCE 700 1- Takeda J. The Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan, JP aut NATIONALLICENCE 700 1- Hanafusa T. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut NATIONALLICENCE 700 1- Matsuzawa Y. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan,, JP aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer