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

Int J Obes Relat Metab Disord. 2001 Apr;25(4):472-7. doi: 10.1038/sj.ijo.0801584.


Objective: To investigate whether genetic variation at the UCP3 locus contributes to human obesity.

Subjects: Ninety-one obese children (BMI>4 standard deviations from age related mean) and 419 Caucasian adults from the Isle of Ely Study.

Design: 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.

Measurements: 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.

Conclusion: 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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anthropometry
  • Body Mass Index*
  • Carrier Proteins / genetics*
  • Child
  • Child, Preschool
  • Cohort Studies
  • European Continental Ancestry Group / genetics*
  • Female
  • Genotype
  • Humans
  • Ion Channels
  • Male
  • Middle Aged
  • Mitochondrial Proteins
  • Mutation, Missense
  • Obesity / blood
  • Obesity / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Promoter Regions, Genetic / genetics*
  • Prospective Studies
  • RNA, Messenger
  • Uncoupling Protein 3
  • United Kingdom


  • Carrier Proteins
  • Ion Channels
  • Mitochondrial Proteins
  • RNA, Messenger
  • UCP3 protein, human
  • Uncoupling Protein 3