Mutations in the glucokinase gene have been identified recently in patients with maturity-onset diabetes of the young, a subtype of NIDDM. The proposed role of glucokinase as a glucose sensor, combined with the low insulin response to glucose found in most Japanese with NIDDM, prompted us to speculate that mutations in the glucokinase gene might be one of the major causes of NIDDM in Japanese subjects. To determine the prevalence of mutations and sequence variations in the glucokinase gene, we screened all 12 exons of the glucokinase gene, including exon/intron junctions, by polymerase chain reaction followed by single-strand conformation polymorphism in 209 Japanese NIDDM subjects. In addition to the mutation in exon 7, which substituted Arg (AGG) for Gly (GGG) at codon 261 (10), a silent mutation of Pro (CCC→CCG) in exon 4 at codon 145 and several new sequence variations in intervening sequences and the 5′-untranslated region of exon 1β (β-cell-specific exon 1) were identified. Because we identified only one subject who had a structurally abnormal glucokinase molecule, we conclude that the prevalence of structural mutations in the glucokinase gene responsible for NIDDM appears to be rare among Japanese patients. To our knowledge, this is the first thorough study describing the ethnic prevalence of mutations and sequence variations in the glucokinase gene in NIDDM.
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Original Articles|
August 01 1993
Sequence Variations of the Glucokinase Gene in Japanese Subjects With NIDDM Free
Kazuhiro Eto;
Kazuhiro Eto
Department of Internal Medicine, Faculty of Medicine, University of Tokyo; and the Institute for Diabetes Care and Research, Asahi Life Foundation
Tokyo, Japan
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Hiroshi Sakura;
Hiroshi Sakura
Department of Internal Medicine, Faculty of Medicine, University of Tokyo; and the Institute for Diabetes Care and Research, Asahi Life Foundation
Tokyo, Japan
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Kotaro Shimokawa;
Kotaro Shimokawa
Department of Internal Medicine, Faculty of Medicine, University of Tokyo; and the Institute for Diabetes Care and Research, Asahi Life Foundation
Tokyo, Japan
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Hiroko Kadowaki;
Hiroko Kadowaki
Department of Internal Medicine, Faculty of Medicine, University of Tokyo; and the Institute for Diabetes Care and Research, Asahi Life Foundation
Tokyo, Japan
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Ryoko Hagura;
Ryoko Hagura
Department of Internal Medicine, Faculty of Medicine, University of Tokyo; and the Institute for Diabetes Care and Research, Asahi Life Foundation
Tokyo, Japan
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Yasuo Akanuma;
Yasuo Akanuma
Department of Internal Medicine, Faculty of Medicine, University of Tokyo; and the Institute for Diabetes Care and Research, Asahi Life Foundation
Tokyo, Japan
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Yashio Yazaki;
Yashio Yazaki
Department of Internal Medicine, Faculty of Medicine, University of Tokyo; and the Institute for Diabetes Care and Research, Asahi Life Foundation
Tokyo, Japan
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Takashi Kadowaki
Takashi Kadowaki
Department of Internal Medicine, Faculty of Medicine, University of Tokyo; and the Institute for Diabetes Care and Research, Asahi Life Foundation
Tokyo, Japan
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Address correspondence and reprint requests to Hiroshi Sakura, MD, The Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7–3-1 Hongo, Bunkyo-ku, Tokyo, Japan 113.
Diabetes 1993;42(8):1133–1137
Article history
Received:
February 18 1993
Revision Received:
April 01 1993
Accepted:
April 01 1993
PubMed:
8325443
Citation
Kazuhiro Eto, Hiroshi Sakura, Kotaro Shimokawa, Hiroko Kadowaki, Ryoko Hagura, Yasuo Akanuma, Yashio Yazaki, Takashi Kadowaki; Sequence Variations of the Glucokinase Gene in Japanese Subjects With NIDDM. Diabetes 1 August 1993; 42 (8): 1133–1137. https://doi.org/10.2337/diab.42.8.1133
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