title: Peroxisome proliferator-activated receptor gamma coactivator 1 alpha promoter polymorphisms are associated with early-onset type 2 diabetes mellitus in the Korean population.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha) is a transcriptional coactivator implicated in insulin release by beta cells and in insulin resistance. Therefore, genetic variation of PPARGC1A could be implicated in the onset of type 2 diabetes. In this study, we examined whether the PPARGC1A gene locus is associated with type 2 diabetes mellitus. We also investigated its association with clinical and metabolic parameters in healthy and diabetic subjects.
  
  
  METHODS
  After sequencing exons and their boundaries of the PPARGC1A gene, including the promoter region ( approximately 1.5 kb), we genotyped eight common single nucleotide polymorphisms (SNPs) in an association study comprising 762 unrelated patients with type 2 diabetes and 303 non-diabetic control patients. We divided the patients with type 2 diabetes into quartiles or three groups according to age at diagnosis of type 2 diabetes (early-onset: <40 years of age, average-onset: 40< or = <60 years, and late-onset: > or =60 years).
  
  
  RESULTS
  There was no strong association between SNPs or haplotypes of PPARGC1A and type 2 diabetes. However, the SNPs of g.-1789G>A and g.-1437C>T were associated with the age at diagnosis of type 2 diabetes (p=0.042 and p=0.032, respectively). In addition, the promoter SNPs of g.-1789G>A and g.-1437C>T and the haplotypes ht2 (-1789A and -1437T) were significantly associated with early-onset type 2 diabetes (p=0.002, p=0.001 and p=0.001, respectively).
  
  
  CONCLUSIONS
  Our results suggest that PPARGC1A promoter polymorphisms are associated with age at diagnosis of type 2 diabetes and early-onset type 2 diabetes in the Korean population.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: H D
authors.initials: HD
authors.lastname: Shin
authors.forename: B L
authors.initials: BL
authors.lastname: Park
authors.forename: Y M
authors.initials: YM
authors.lastname: Cho
authors.forename: S Y
authors.initials: SY
authors.lastname: Kim
authors.forename: H K
authors.initials: HK
authors.lastname: Lee
authors.forename: K S
authors.initials: KS
authors.lastname: Park
mesh_terms: D017668:Age of Onset; D000368:Aged; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007723:Korea; D015810:Linkage Disequilibrium; D008875:Middle Aged; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors