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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

International Journal of Obesity volume 25, pages 472–477 (2001)Cite this article

Abstract

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.

International Journal of Obesity (2001) 25, 472–477

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Authors and Affiliations

  1. University Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, UK

    DJ Halsall, IS Farooqi, J Keogh & S O'Rahilly

  2. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, UK

    J Luan & NJ Wareham

  3. Section of Endocrinology, Imperial College School of Medicine, London, UK

    P Saker

  4. International Diabetes Institute, Caulfield, Victoria, Australia

    S Huxtable

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  1. DJ Halsall
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  2. J Luan
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  8. S O'Rahilly
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Correspondence to DJ Halsall.

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Halsall, D., Luan, J., Saker, P. et al. 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 25, 472–477 (2001). https://doi.org/10.1038/sj.ijo.0801584

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