title: Analysis of the peroxisome proliferator activated receptor gamma (PPARgamma) gene in HAIRAN syndrome with obesity.
abstract: OBJECTIVE
  To test the hypothesis that the triad of hyperandrogenism, insulin resistance and acanthosis nigricans (HAIRAN syndrome) in the presence of obesity, also known as type C insulin resistance, is caused by mutations in the gene for peroxisome proliferator activated receptor gamma (PPARgamma), a receptor for the thiazolidinedione drugs that enhance sensitivity to insulin. To investigate possible correlations between mutations in PPARgamma and the degree of insulin resistance.
  
  
  METHODS
  A candidate gene approach to study the molecular basis for a syndrome of obesity; a comparison of genotype with in vivo phenotype.
  
  
  METHODS
  Fifteen unrelated patients with HAIRAN syndrome and obesity. Controls for the gene analysis: 25 unrelated non-diabetic non-obese individuals. Controls for the metabolic studies: six unrelated patients with type 2 diabetes mellitus and nine unrelated non-diabetic non-obese individuals.
  
  
  METHODS
  Analysis of polymerase chain reaction (PCR) products of the 7 exons that constitute the entire coding region of both PPARgamma isoforms (PPARgamma1 and PPARgamma2) for single-stranded conformational polymorphisms (SSCP); in exons with variant patterns: restriction fragment length polymorphism (RFLP) analysis; and, where relevant, direct sequencing. Evaluation of insulin resistance using the insulin euglycaemic clamp technique.
  
  
  RESULTS
  A synonymous substitution in codon 477 (CACHis --> CATHis) was found in one patient. A missense mutation in codon 12 of PPARgamma2 (CCAPro --> GCAAla) was found in another patient, but not in any of 25 non-diabetic, non-obese control individuals. The patient with the Pro12Ala variant had the highest steady state glucose infusion rate (SSGIR) and most marked suppression of hepatic glucose production rate (HGPR) of all of the patients studied.
  
  
  CONCLUSIONS
  Mutations in the PPARgamma gene are unlikely to be major contributors to HAIRAN syndrome with obesity. The Pro12Ala variant may correlate with a lesser degree of insulin resistance in these patients.
authors.affiliation: Institute of Endocrinology, Diabetes & Metabolism, Rambam Medical Centre and B. Rappaport Faculty of Medicine Technion, Haifa, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Globerman
authors.forename: Y
authors.initials: Y
authors.lastname: Zauberman
authors.forename: T
authors.initials: T
authors.lastname: Makarov
authors.forename: B A
authors.initials: BA
authors.lastname: Beamer
authors.forename: C J
authors.initials: CJ
authors.lastname: Yen
authors.forename: A R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: C
authors.initials: C
authors.lastname: Harel
authors.forename: E
authors.initials: E
authors.lastname: Karnieli
mesh_terms: D000052:Acanthosis Nigricans / Q000235:genetics*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D017588:Hyperandrogenism / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D020033:Protein Isoforms / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D005947:Glucose