A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans (original) (raw)

References

1. Fleury, C. et al. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nature Genet. 15, 269–272 (1997).
   Article CAS Google Scholar
2. Gimeno, R.E. et al. Cloning and characterization of an uncoupling protein homolog: a potential molecular mediator of human thermogenesis. Diabetes 46, 900–906 (1997).
   Article CAS Google Scholar
3. Jaburek, M. et al. Transport function and regulation of mitochondrial uncoupling proteins 2 and 3. J. Biol. Chem. 274, 26003–26007 (1999).
   Article CAS Google Scholar
4. Bouchard, C., Perusse, L., Chagnon, Y.C., Warden, C. & Ricquier, D. Linkage between markers in the vicinity of the uncoupling protein 2 gene and resting metabolic rate in humans. Hum. Mol. Genet. 6, 1887–1889 (1997).
   Article CAS Google Scholar
5. Ricquier, D. & Bouillaud, F. The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochem. J. 345, 161–179 (2000).
   Article CAS Google Scholar
6. Boss, O., Hagen, T. & Lowell, B.B. Uncoupling proteins 2 and 3: potential regulators of mitochondrial energy metabolism. Diabetes 49, 143–156 (2000).
   Article CAS Google Scholar
7. Oberkofler, H. et al. Uncoupling protein-2 gene: reduced mRNA expression in intraperitoneal adipose tissue of obese humans. Diabetologia 41, 940–946 (1998).
   Article CAS Google Scholar
8. Walder, K. et al. Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism/obesity in Pima indians. Hum. Mol. Genet. 7, 1431–1435 (1998).
   Article CAS Google Scholar
9. Dalgaard, L.T., Sorensen, T.I., Andersen, T., Hansen, T. & Pedersen, O. An untranslated insertion variant in the uncoupling protein 2 gene is not related to body mass index and changes in body weight during a 26-year follow-up in Danish Caucasian men. Diabetologia 42, 1413–1416 (1999).
   Article CAS Google Scholar
10. Pecqueur, C. et al. Uncoupling protein 2, in vivo distribution, induction upon oxidative stress, and evidence for translational regulation. J. Biol. Chem. 276, 8705–8712 (2001).
    Article CAS Google Scholar
11. Vaulont, S., Vasseur-Cognet, M. & Kahn, A. Glucose regulation of gene transcription. J. Biol. Chem. 275, 31555–31558 (2000).
    Article CAS Google Scholar
12. Rosenbaum, M., Leibel, R.L. & Hirsch, J. Obesity. N. Engl. J. Med. 337, 396–407 (1997).
    Article CAS Google Scholar
13. Ravussin, E. et al. Reduced rate of energy expenditure as a risk factor for body-weight gain. N. Engl. J. Med. 318, 467–472 (1988).
    Article CAS Google Scholar
14. Li, B. et al. Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice. Nature Med. 6, 1115–1120 (2000).
    Article CAS Google Scholar
15. Kopecky, J., Clarke, G., Enerback, S., Spiegelman, B. & Kozak, L.P. Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity. J. Clin. Invest. 96, 2914–2923 (1995).
    Article CAS Google Scholar
16. Kozak, L.P. Uncoupling diet and diabetes. Nature Med. 6, 1092–1093 (2000).
    Article CAS Google Scholar
17. Otabe, S. et al. A genetic variation in the 5′ flanking region of the UCP3 gene is associated with body mass index in humans in interaction with physical activity. Diabetologia 43, 245–249 (2000).
    Article CAS Google Scholar
18. Cassell, P.G. et al. Evidence that single nucleotide polymorphism in the uncoupling protein 3 (UCP3) gene influences fat distribution in women of European and Asian origin. Diabetologia 43, 1558–1564 (2000).
    Article CAS Google Scholar
19. Schrauwen, P., Xia, J., Walder, K., Snitker, S. & Ravussin, E. A novel polymorphism in the proximal UCP3 promoter region: effect on skeletal muscle UCP3 mRNA expression and obesity in male non-diabetic Pima Indians. Int. J. Obes. Relat. Metab. Disord. 23, 1242–1245 (1999).
    Article CAS Google Scholar
20. Argyropoulos, G. et al. Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes. J. Clin. Invest. 102, 1345–1351 (1998).
    Article CAS Google Scholar
21. Kiefer, I., Kunze, U., Mitsche, N. & Kunze, M. Obesity in Austria: epidemiologic and social medicine aspects. Acta Med. Austriaca. 25, 126–128 (1998).
    CAS PubMed Google Scholar
22. Esterbauer, H. et al. Uncoupling protein-3 gene expression: reduced skeletal muscle mRNA in obese humans during pronounced weight loss. Diabetologia 42, 302–309 (1999).
    Article CAS Google Scholar
23. Esterbauer, H., Oberkofler, H., Krempler, F., Strosberg, A.D. & Patsch, W. The uncoupling protein-3 gene is transcribed from tissue-specific promoters in humans but not in rodents. J. Biol. Chem. 275, 36394–36399 (2000).
    Article CAS Google Scholar
24. Zilberfarb, V. et al. Human immortalized brown adipocytes express functional beta3-adrenoceptor coupled to lipolysis. J. Cell Sci. 110, 801–807 (1997).
    CAS PubMed Google Scholar
25. Chiano, M.N. & Clayton, D.G. Fine genetic mapping using haplotype analysis and the missing data problem. Ann. Hum. Genet. 62, 55–60 (1998).
    Article CAS Google Scholar
26. Mander, A.P. & Clayton, D.G. Haplotype frequency estimation using an EM algorithm and log-linear modelling. Stata Tech. Bull. 55, 10–12 (2000).
    Google Scholar
27. Terwilliger, J.D. & Ott, J. Handbook of Human Genetic Linkage (Johns Hopkins University Press, Baltimore, 1994).
    Google Scholar
28. Robins, J., Greenland, S. & Breslow, N.E. A general estimator for the variance of the Mantel-Haenszel odds ratio. Am. J. Epidemiol. 124, 719–723 (1986).
    Article CAS Google Scholar
29. Bradburn, M.J., Deeks, J.J. & Altman D.G. Metan – an alternative meta-analysis command. Stata Tech. Bull. 44, 4–15 (1998).
    Google Scholar
30. Heinemeyer, T. et al. Expanding the TRANSFAC database towards an expert system of regulatory molecular mechanisms. Nucl. Acids Res. 27, 318–322 (1999).
    Article CAS Google Scholar

Download references