title: Novel mutation in the adiponectin (ADIPOQ) gene is associated with hypoadiponectinaemia in Japanese-Brazilians.
abstract: OBJECTIVE
  Adiponectin is an important mediator of insulin sensitivity, encoded by the ADIPOQ gene. Here we describe two Japanese-Brazilian families with hypoadiponectinaemia due to a novel mutation in ADIPOQ.
  
  
  METHODS
  In this study, we examined the entire translated regions of adiponectin in Japanese-Brazilians, a population with one of the highest prevalence rates of diabetes worldwide. We screened 200 patients with type 2 diabetes (DM) and 240 age-matched subjects with normal glucose tolerance.
  
  
  RESULTS
  A novel heterozygous T deletion at position 186 in exon 2 of ADIPOQ, causing a frameshift at codon 62 and leading to a premature termination at codon 168 (p.Gly63ValfsX106), was found in two individuals with diabetes. This mutation was not found in 240 nondiabetic control subjects. In addition, we screened the mutation in an expanded set of 100 nondiabetic subjects from the general Brazilian population, but we found no mutations. In addition, six family members of the probands were identified as mutation-carriers. Individuals who were mutation-carriers had markedly low plasma adiponectin concentrations compared with those without the mutation [DM: 0.65 (0.59-1.34) microg/ml vs. 5.30 (3.10-8.55) microg/ml, P < 0.0001; normal glucose tolerance: 0.95 (0.76-1.48) microg/ml vs. 8.50 (5.52-14.55) microg/ml, P = 0.003]. All individuals carrying the p.Gly63ValfsX106 mutation and older than 30 years were found to be diabetic.
  
  
  CONCLUSIONS
  We describe for the first time a frameshift mutation in exon 2 of the ADIPOQ gene, which modulates adiponectin levels and may contribute to the genetic risk of late-onset diabetes in Japanese-Brazilians.
authors.affiliation: Department of Medicine, Division of Endocrinology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Marcio F
authors.initials: MF
authors.lastname: Vendramini
authors.forename: Teresa S
authors.initials: TS
authors.lastname: Kasamatsu
authors.forename: Felipe
authors.initials: F
authors.lastname: Crispim
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Ferreira
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Matioli
authors.forename: Regina S
authors.initials: RS
authors.lastname: Moisés
mesh_terms: D052242:Adiponectin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree
chemical_list: D052242:Adiponectin