title: Adiponectin receptor genes: mutation screening in syndromes of insulin resistance and association studies for type 2 diabetes and metabolic traits in UK populations.
abstract: OBJECTIVE
  Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. Several reports suggest that genetic variants in the adiponectin gene are associated with circulating levels of adiponectin, insulin sensitivity and type 2 diabetes risk. Recently two receptors for adiponectin have been cloned. Genetic studies have yielded conflicting results on the role of these genes and type 2 diabetes predisposition. In this study we aimed to evaluate the potential role of genetic variation in these genes in syndromes of severe insulin resistance, type 2 diabetes and in related metabolic traits in UK Europid populations.
  
  
  METHODS
  Exons and splice junctions of the adiponectin receptor 1 and 2 genes (ADIPOR1; ADIPOR2) were sequenced in patients from our severe insulin resistance cohort (n=129). Subsequently, 24 polymorphisms were tested for association with type 2 diabetes in population-based type 2 diabetes case-control studies (n=2,127) and with quantitative traits in a population-based longitudinal study (n=1,721).
  
  
  RESULTS
  No missense or nonsense mutations in ADIPOR1 and ADIPOR2 were detected in the cohort of patients with severe insulin resistance. None of the 24 polymorphisms (allele frequency 2.3-48.3%) tested was associated with type 2 diabetes in the case-control study. Similarly, none of the polymorphisms was associated with fasting plasma insulin, fasting and 2-h post-load plasma glucose, 30-min insulin increment or BMI.
  
  
  CONCLUSIONS
  Genetic variation in ADIPOR1 and ADIPOR2 is not a major cause of extreme insulin resistance in humans, nor does it contribute in a significant manner to type 2 diabetes risk and related traits in UK Europid populations.
authors.affiliation: Metabolic Disease Group, The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Collins
authors.forename: J
authors.initials: J
authors.lastname: Luan
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: A
authors.initials: A
authors.lastname: Daly
authors.forename: R K
authors.initials: RK
authors.lastname: Semple
authors.forename: S
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: N J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: I
authors.initials: I
authors.lastname: Barroso
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005091:Exons; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics*; D018570:Risk Assessment; D006113:United Kingdom / Q000453:epidemiology
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface