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Horm Metab Res 2003; 35(5): 308-312
DOI: 10.1055/s-2003-41307
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Identification of a Novel Variant in the Phosphoenolpyruvate Carboxykinase Gene Promoter in Japanese Patients with Type 2 Diabetes

Y.  Horikawa1 , T.  Yamasaki1 , H.  Nakajima1 , R.  Shingu1 , I.  Yoshiuchi1 , J.  Miyagawa1 , M.  Namba1 , T.  Hanafusa1 , Y.  Matsuzawa1
  • 1Department of Internal Medicine and Molecular Science, Graduate School of Medicine, B5, Osaka University (2 - 2 Yamada-Oka, Suita, Osaka 565-0871, Japan)
Further Information

Publication History

Received 2 August 2002

Accepted after Revision 16 December 2002

Publication Date:
13 August 2003 (online)

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Abstract

Phosphoenolpyruvate carboxykinase (PEPCK) plays an important role in gluconeogenesis and hepatic glucose production. To test the hypothesis that mutations of the PEPCK gene promoter contribute to the increased hepatic glucose production that leads to diabetes, we screened for polymorphisms of the PEPCK promoter region in 252 Japanese type 2 diabetic patients and 188 non-diabetic control subjects. A novel variant at position - 232 (C to G) was found at a similar frequency in type 2 diabetes patients (32 %) and control subjects (35 %) (p = 0.26). However, patients with the - 232 G/G genotype had an earlier age of onset than those with the - 232 C/C or - 232 C/G genotypes (p = 0.028). As the variant might well otherwise influence hormonal action, we transfected PEPCK-luciferase fusion gene constructs with the variant into human hepatoma cells and examined the response to dexamethasone, insulin, and cAMP. The reporter assay showed no significant difference in hormonal responses with the fusion gene containing the variant. Accordingly, the single-base variant at position - 232 of the PEPCK gene promoter is most probably not a major contributor to the pathogenesis of type 2 diabetes. However, this variation may be useful as a genetic marker for other metabolic disorders, especially in Japanese.

Key words:

Gluconeogenesis - Single Nucleotide Polymorphism - Insulin Response - Single Strand Conformation Polymorphism - Gene Expression

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Y. Horikawa, M.D. 

The Laboratory of Molecular Genetics · Department of Cell Biology · Institute for Molecular and Cellular Regulation · Gunma University

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