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

Diabetologia. 2002 May;45(5):740-3. doi: 10.1007/s00125-002-0803-z. Epub 2002 Apr 23.


Aims/hypothesis: Peroxisome proliferator activated receptor gamma coactivator-1 (PGC-1), a transcriptional coactivator of the nuclear receptor PPARgamma, 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 Thr394Thr - Gly482Ser 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA Primers
  • Diabetes Mellitus, Type 2 / genetics*
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Glycated Hemoglobin / analysis
  • Haplotypes
  • Heat-Shock Proteins / genetics*
  • Humans
  • Insulin Resistance / genetics*
  • Japan
  • Middle Aged
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Reference Values
  • Transcription Factors / genetics*
  • White People


  • DNA Primers
  • Glycated Hemoglobin A
  • Heat-Shock Proteins
  • Transcription Factors
  • peroxisome-proliferator-activated receptor-gamma coactivator-1