title: A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hara
authors.forename: K
authors.initials: K
authors.lastname: Tobe
authors.forename: T
authors.initials: T
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Kadowaki
authors.forename: Y
authors.initials: Y
authors.lastname: Akanuma
authors.forename: C
authors.initials: C
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Kadowaki
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006442:Glycated Hemoglobin / Q000032:analysis; D006239:Haplotypes; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007564:Japan; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D014157:Transcription Factors / Q000235:genetics*; D044465:White People
chemical_list: D017931:DNA Primers; D006442:Glycated Hemoglobin; D006360:Heat-Shock Proteins; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1