Diabetologia

, Volume 45, Issue 5, pp 740–743

A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes

  • K. Hara
  • K. Tobe
  • T. Okada
  • H. Kadowaki
  • Y. Akanuma
  • C. Ito
  • S. Kimura
  • T. Kadowaki
Article

Abstract

Aims/hypothesis. Peroxisome proliferator activated receptor γ coactivator-1 (PGC-1), a transcriptional coactivator of the nuclear receptor PPARγ, plays a role in adaptive thermogenesis and insulin sensitivity. Plasma fasting insulin has been linked to the chromosomal region where the PGC-1 gene is located. Thus, PGC-1 can be viewed as a functional and positional candidate for the susceptibility gene for Type II (non-insulin-dependent) diabetes mellitus.

Methods. After screening the PGC-1 gene for single nucleotide polymorphisms (SNPs), we performed an association study using the newly detected SNPs in 537 Type II diabetic patients and 417 non-diabetic subjects.

Results. We found three relatively frequent SNPs in the PGC-1 gene (IVS4-11T > C, Thr394Thr and Gly482Ser). There were significant differences in fasting insulin (Gly/Gly; 37.7 ± 1.43, Gly/Ser; 40.2 ± 1.21, Ser/Ser; 44.3 ± 1.82 pmol/l, p = 0.018) and insulin resistance index (Gly/Gly; 1.48 ± 0.06, Gly/Ser; 1.56 ± 0.05, Ser/Ser; 1.75 ± 0.08, p = 0.027) according to the genotype of the Gly482Ser polymorphism. The Thr394ThrGly482Ser haplotype was associated with Type II diabetes (p = 0.00003).

Conclusion/interpretation. The results of this study suggested that the PGC-1 gene might be implicated in the pathogenesis of Type II diabetes.

Single nucleotide polymorphism HOMA transcriptional coactivator susceptibility gene association study direct sequencing linkage disequilibrium haplotype PCR-RFLP 

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • K. Hara
    • 1
  • K. Tobe
    • 1
  • T. Okada
    • 1
  • H. Kadowaki
    • 3
  • Y. Akanuma
    • 2
  • C. Ito
    • 5
  • S. Kimura
    • 1
  • T. Kadowaki
    • 1
  1. 1.Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655Japan
  2. 2.CREST, Japan Science and Technology Corporation (JST), Chuo-ku, TokyoJapan
  3. 3.The Institute for Diabetes Care and Research, Asahi Life Foundation, TokyoJapan
  4. 4.Department of Metabolic Disorder, Research Institute, International Medical Center of Japan, TokyoJapan
  5. 5.Hiroshima Atomic Bomb Casualty Council Health Management Center, HiroshimaJapan

Personalised recommendations