title: Uncoupling protein 3 genetic variants in human obesity: the c-55t promoter polymorphism is negatively correlated with body mass index in a UK Caucasian population.
abstract: OBJECTIVE
  To investigate whether genetic variation at the UCP3 locus contributes to human obesity.
  
  
  METHODS
  Ninety-one obese children (BMI>4 standard deviations from age related mean) and 419 Caucasian adults from the Isle of Ely Study.
  
  
  METHODS
  Single strand conformation polymorphism (SSCP) analysis was used to scan the coding region of the UCP3 gene in 91 severely obese children. A common polymorphism identified in this gene (c-55t) has been shown to associate with lower UCP3 mRNA expression. Polymerase chain reaction-based forced restriction digestion was used to detect this allele in Caucasian adults. Multiple regression analysis was used to determine associations between the c-55t genotype and anthropometric, energetic and biochemical indices relevant to obesity.
  
  
  METHODS
  For the obese children, SSCP analysis and sequencing of variants were carried out. For the Isle of Ely Study, c-55t genotype and anthropometric (body mass index, waist-hip ratio, percentage body fat), energetic (dietary fat intake, physical activity index, adjusted metabolic rate, maximum oxygen consumption) and biochemical indices (pre- and post-glucose challenge plasma triglycerides, non-esterified fatty acids, insulin and glucose) were determined.
  
  
  RESULTS
  A previously reported missense mutation (V102I) was detected in a single obese Afro-Carribean child. Twenty-one percent of the genes examined in the Isle of Ely study carried the c-55t promoter variant. Age-adjusted body mass index (BMI) was significantly (P=0.0037) lower in carriers of this variant.
  
  
  CONCLUSIONS
  Mutations in the coding sequence of UCP3 are unlikely to be a common monogenic cause of severe human obesity. In a Caucasian population the UCP3 c-55t polymorphism is negatively associated with BMI.
authors.affiliation: University Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, UK. djh44@hermes.cam.ac.uk
authors.forename: D J
authors.initials: DJ
authors.lastname: Halsall
authors.forename: J
authors.initials: J
authors.lastname: Luan
authors.forename: P
authors.initials: P
authors.lastname: Saker
authors.forename: S
authors.initials: S
authors.lastname: Huxtable
authors.forename: I S
authors.initials: IS
authors.lastname: Farooqi
authors.forename: J
authors.initials: J
authors.lastname: Keogh
authors.forename: N J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: S
authors.initials: S
authors.lastname: O'Rahilly
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000886:Anthropometry; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007473:Ion Channels; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D020125:Mutation, Missense; D009765:Obesity / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012333:RNA, Messenger; D000071247:Uncoupling Protein 3; D006113:United Kingdom; D044465:White People / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3