Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-22T23:20:52.995Z Has data issue: false hasContentIssue false
  • English
  • Français

Obesity — a genetic disease of adipose tissue?

Published online by Cambridge University Press:  09 March 2007

Peter Arner
Peter Arner*
Affiliation:
Karolinska Institute, Department of Medicine, CME, M61, Huddinge Hospital, S-141 86 Huddinge, Stockholm, Sweden
*
*Corresponding author: P. Arner, fax +46 8 58582407, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Although the rapid increase in the prevalence of obesity in many countries suggests that environmental factors (mainly overeating and physical inactivity) play the most important role in the development of overweight, it is very likely that genetic factors also contribute. It appears that one major gene in combination with one or several minor genes constitute the genetic components behind excess accumulation of body fat in most obese individuals. However, monogenic obesity has been described in a few families due to changes in leptin, leptin receptor, prohormone convertase, pro-opiomelanocortin or melanocortin-4 receptor. None of the monogenic variants is of great importance for common human obesity; the latter genes are unknown so far. Results from genomic scans suggest that major obesity genes are located on chromosomes 2, 10, 11 and 20. Studies of candidate genes indicate that the minor obesity genes control important functions of adipose tissue, and that structural variance in these genes may alter adipose tissue function in a way that promotes obesity. Such genes are β2- and β3-adrenoceptors, hormone-sensitive lipase, tumour necrosis factor alpha, uncoupling protein-1, low-density lipoprotein receptor, and peroxisome proliferator activator receptor gamma-2. Some of these genes may promote obesity by gene–gene interactions (for example β3-adrenoceptors and uncoupling protein-1) or gene–environment interactions (for example β2-adrenoceptors and physical activity). Some are important for obesity only among women (for example β2- and β3-adrenoceptors, low-density lipoprotein receptor and tumour necrosis factor alpha). Few ‘non-adipose’ genes have so far shown a firm association to common human obesity, which could suggest that the important genes for the development of excess body fat also control adipose tissue function.

Keywords

Fat cellsBody mass indexLipolysisThermogenesisAdipocyte differentiation
Type
Research Article
Information
British Journal of Nutrition , Volume 83 , Issue S1 , June 2000 , pp. S9 - S16
Copyright
Copyright © The Nutrition Society 2000

References

Allison, DB, Kaprio, J, Korkeila, M, Koskenvuo, M, Neale, MC & Kayakawa, K (1996) The heritability of body mass index among an international sample of monozygotic twins reared apart. International Journal of Obesity 20, 501–506.Google ScholarPubMed
Allison, DB, Heo, M, Faith, MS & Pietrobelli, A (1998) Meta-analysis of the associaton of the Trp64Arg polymorphism in the β3-adrenergic receptor with body mass index. International Journal of Obesity 22, 559–566.CrossRefGoogle Scholar
Arner, P & Hoffstedt, F (1999) Adrenoceptor genes in human obesity. Journal of Internal Medicine 6, 667–672.CrossRefGoogle Scholar
Bouchard, C (1993) Genes and body fat. American Journal of Human Biology 5, 425–432.CrossRefGoogle Scholar
Bouchard, C, Pérusse, L (1996) Current status of the human obesity gene map. Obesity Research 4, 81–90.CrossRefGoogle ScholarPubMed
Buscher, R, Herrmann, V & Insel, PA (1999) Human adrenoceptor polymorphisms: evolving recognition of clinical importance. Trends in Pharmacological Sciences 20, 94–99.CrossRefGoogle Scholar
Cagnon, J, Lago, F, Chagnon, YC, Pérusse, L, Näslund, I, Lissner, L, Sjöström, L & Bouchard, C (1998) DNA polymorphism in the uncoupling protein 1 (UCP1) gene has no effect on obesity related phenotypes in the Swedish obese subjects cohorts. International Journal of Obesity 22, 500–505.Google Scholar
Cannon, B, Houstek, J & Nedergaard, J (1998) Brown adipose tissue. More than an effector of thermogenesis?. Annals of New York Academy of Science 856, 171–187.CrossRefGoogle Scholar
Carpene, C, Bousquet-Melou, A, Galitzky, J, Berlan, M & Lafontan, M (1998) Lipolytic effects of beta1-, beta2- and beta3-adrenergic agonists in white adipose tissue of mammals. Annals of New York Academy of Science 839, 186–189.CrossRefGoogle Scholar
Cassard-Doulcier, AM, Bouillaud, F, Chagnon, M, Gelly, C, Dionne, FT, Oppert, JM, Bouchard, C, Chagnon, Y & Ricquier, D (1996) The BclI polymorphism of the human uncoupling protein (UCP) gene is due to a point mutation in the 5′ flanking region. International Journal of Obesity 3, 278–279.Google Scholar
Chagnon, YC, Pérusse, L & Bouchard, C (1998) The human obesity gene map: the 1997 update. Obesity Research 6, 76–92.CrossRefGoogle ScholarPubMed
Chua, S & Leibel, RL (1997) Obesity genes. Molecular and metabolic mechanisms. Diabetes Reviews 5, 2–7.Google Scholar
Clément, K, Ruiz, J, Cassard-Doulcier, AM, Bouillaud, R, Ricquier, D, Basdevant, A, Guy-Grand, B & Froguel, P (1996) Additive effect of A G (-3826) variant of the uncoupling protein gene and the Trp64Arg mutation of the beta3-adrenergic gene on weight gain in morbid obesity. International Journal of Obesity 12, 1062–1066.Google Scholar
Clément, K, Vaiesse, C, Lahlou, N, Cabrol, S, Pelbux, V, Cassuto, D, Gourmelen, M, Dina, C, Chambay, J, Lacorte, JM, Basdevant, A, Bougneres, P, Lebouc, Y, Frougel, P, Guy-Grand, B (1998) A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 6674, 398–401.CrossRefGoogle Scholar
Clément, K, Dina, C, Basdevant, A, Chastang, N, Pelloux, V, Lahlou, N, Berlan, M, Langin, D, Guy-Grand, B & Frougel, P (1999) A sib-pair analysis study of 15 candidate genes in French families with morbid obesity. Diabetes 48, 398–402.CrossRefGoogle ScholarPubMed
Comuzzie, AG & Allison, DB (1998) The search for human obesity genes. Science 280, 1374–1377.CrossRefGoogle ScholarPubMed
Comuzzie, AG, Hixson, JE, Almasy, L, Mitchell, BD, Mahaney, MC, Dyer, TD, Stern, MP, MacCluer, JW & Blangero, J (1997) A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2. Nature Genetics 15, 273–276.CrossRefGoogle Scholar
Deeb, SS, Fajas, L, Nemoto, M, Pihlajamäki, J, Mykkänen, L, Kuusisto, J, Laakso, M, Fujimoto, W & Auwerx, J (1998) A Pro12Ala substitution in PPARγ-2 with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nature Genetics 20, 284–287.CrossRefGoogle Scholar
Descamps, O, Bilheimer, D & Herz, J (1993) Insulin stimulates receptor-mediated uptake of apoE-enriched lipoproteins and activated alpha 2-macroglobulin in adipocytes. Journal of Biological Chemistry 2, 974–981.CrossRefGoogle Scholar
Echwald, SM, Sörensen, TIA, Tybjaerg-Hansen, A, Andersen, T & Pedersen, O (1998) Gln 27Glu variant of the human β2-adrenoceptor gene is not associated with early-onset obesity in Danish men. Diabetes 47, 1657–1658.CrossRefGoogle Scholar
Echwald, SM, Sörensen, TIA, Andersen, T, Tubjaerg-Hansen, A, Clausen, JO & Pedersen, O (1999) Mutational analysis of the proopiomelanocortin gene in Caucasians with early onset obesity. International Journal of Obesity 23, 293–298.CrossRefGoogle ScholarPubMed
Ek, J, Urhammer, SA, Sörensen, TIA, Andersen, T, Auwerz, J & Pedersen, O (1999) Homozygosity of the Pro12Ala variant of the peroxisome proliferation-activated receptor-γ-2 (PPARγ-2): divergent modulating effects on body mass index in obese and lean Caucasian men. Diabetologia 42, 892–895.CrossRefGoogle Scholar
Férnandez-Real, JM, Gutierrez, C, Ricart, W, Casamitjana, R, Fernández-Castaner, M, Vendrell, J, Richart, C & Soler, J (1997) The TNF–α gene Nco I polymorphism influences the relationship among insulin resistance, percent body fat and increased serum leptin levels. Diabetes 46, 1468–1472.CrossRefGoogle Scholar
Fogelholm, M, Valve, R, Kukkonne-Harjula, K, Nenonen, A, Hakkarainen, V, Laakso, M & Uusitupa, M (1998) Additive effects of the mutations in the β3-adrenergic receptor and uncoupling protein-1 genes on weight loss and weight maintenance in Finnish women. Journal of Clinical Endocrinology Metabolism 83, 4246–4250.Google ScholarPubMed
Fujisawa, T, Ikegami, H, Kwaguchi, Y & Ogihara, T (1998) Meta-analysis of the association of Trp64Arg polymorphism of β3-adrenergic receptor gene with body mass index. Journal of Clinical Endocrinology and Metabolism 83, 2441–2444.Google Scholar
Fumeron, F, Durack-Bown, I, Betoulle, D, Cassard-Doulcier, AM, Tuzet, S, Bouillaud, F, Melchior, JC, Ricquier, D & Apfelbaum, M (1996) Polymorphisms of uncoupling protein (UCP) and beta3-adrenoceptor genes in obese people submitted to a low calorie diet. International Journal of Obesity 12, 1051–1054.Google Scholar
Gasic, S, Tian, B & Green, A (1999) Tumor necrosis factor-alpha stimulates lipolysis in adipocytes by decreased Gi protein concentrations. Journal of Biological Chemistry 10, 6770–6775.CrossRefGoogle Scholar
Ginsburg, E, Livshits, G, Yakovenko, K & Kobyliansky, E (1998) Major gene control of human body height, weight and BMI in five ethnically different populations. Annals of Human Genetics 62, 307–322.CrossRefGoogle ScholarPubMed
Gu, Z, Hillier, L, Kowk, P-Y (1998) Single nucleotide polymorphism hunting in cyberspace. Human Mutation 12, 221–225.3.0.CO;2-I>CrossRefGoogle ScholarPubMed
Häger, J, Dina, C, Francke, S, Dubouis, S, Houari, M, Vatin, V, Vaillant, E, Lorentz, N, Basdevant, A, Clement, K, Guy-Grand, B & Frougel, P (1998) A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10. Nature Genetics 20, 304–308.CrossRefGoogle Scholar
Hellström, L, Langin, D, Reynisdottir, S, Dauzats, M & Arner, P (1996) Adipocyte lipolysis in normal weight subjects with obesity among first-degree relatives. Diabetologia 8, 921–928.CrossRefGoogle Scholar
Hellström, L, Large, V, Reynisdottir, S, Wahrenberg, H & Arner, P (1999) The different effects of Gln27Glu beta2-adrenoceptor gene polymorphism on obesity in males and females. Journal of Internal Medicine 3, 253–259.CrossRefGoogle Scholar
Herrmann, SM, Ricard, S, Nicaud, V, Mallet, C, Arveilert, D, Evans, A, Ruidavets, JB, Luc, G, Bara, L, Parra, HJ, Poirier, O & Cambien, F (1998) Polymorphisms of the tumour necrosis factor-α gene, coronary heart disease and obesity. European Journal of Clinical Investigation 28, 59–66.CrossRefGoogle ScholarPubMed
Hill, JO & Peters, JC (1998) Environmental contributions to the obesity epidemic. Science 280, 1371–1374.CrossRefGoogle Scholar
Hoffstedt, J, Eriksson, P, Hellström, L, Rössner, S, Rydén, M & Arner, P (2000) Excessive fat accumulation is associated with the TNF-α -308 G/A promoter polymorphism in women but not in men. Diabetologia 43, 117–120.CrossRefGoogle Scholar
Hoffstedt, J, Poirier, O, Thörne, A, Lönnqvist, F, Herrmann, SM, Cambien, F & Arner, P (1999) Polymorphism of the human β3-adrenoceptor gene forms a well-conserved haplotype that is associated with moderate obesity and altered receptor function. Diabetes 48, 203–205.CrossRefGoogle ScholarPubMed
Hotamisligil, GS (1999) Mechanisms of TNF-alpha-induced insulin resistance. Experimental Clinical Endocrinology and Diabetes 107, 119–125.CrossRefGoogle ScholarPubMed
Hotamisligil, GS & Spiegelman, BM (1994) Tumor necrosis factor alpha: a key component of the obesity–diabetes link. Diabetes 43, 1271–1278.CrossRefGoogle ScholarPubMed
Ishiyama-Shigemoto, S, Yamada, K, Yuan, X, Ichikawa, E & Nonaka, K (1999) Association of polymorphisms in the β2-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetes mellitus. Diabetologia 42, 98–101.CrossRefGoogle Scholar
Jackson, RS, Creemers, JW, Ohagi, S, Raffin-Sanson, ML, Sanders, L, Montague, CT, Hutton, JC, O'Rahilly, S (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nature Genetics 3, 303–306.CrossRefGoogle Scholar
Katzmarzyk, P, Pérusse, L & Bouchard, C (1999) Genetics of abdominal visceral fat levels. American Journal of Human Biology 11, 225–235.3.0.CO;2-J>CrossRefGoogle ScholarPubMed
Klannemark, M, Orho, M, Langin, D, Laurell, H, Holm, C, Reynisdottir, S, Arner, P & Groop, L (1998) The putative role of the hormone-sensitive lipase gene in the pathogenesis in type II diabetes mellitus and abdominal obesity. Diabetologia 41, 1516–1522.CrossRefGoogle ScholarPubMed
Krief, S, Lönnqvist, F, Raimbault, S, Baude, B, van Spronsen, A, Arner, P, Strosberg, AD, Ricquier, D & Emorine, LJ (1993) Tissue distribution of beta3-adrenergic receptor mRNA in man. Journal of Clinical Investigation 91, 344–349.CrossRefGoogle Scholar
Krude, H, Biebergmann, H, Luck, W, Horn, R, Brabant, C & Gruters, A (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nature Genetics 2, 155–157.CrossRefGoogle Scholar
Langin, D, Holm, C & Lafontan, M (1996) Adipocyte hormone sensitive lipase: a major regulator of lipid metabolism. Proceedings of the Nutrition Society 55, 93–109.CrossRefGoogle Scholar
Large, V & Arner, P (1998) Regulation of lipolysis in humans. Pathophysiological modulation in obesity, diabetes and hyperlipidaemia. Diabetes and Metabolism 5, 409–418.Google Scholar
Large, V, Hellström, L, Reynisdottir, S, Lönnqvist, F, Eriksson, P, Lannfelt, L & Arner, P (1997) Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function. Journal of Clinical Investigation 100, 3005–3013.CrossRefGoogle ScholarPubMed
Large, V, Reynisdottir, S, Langin, D, Fredby, K, Klannemark, M, Holm, C & Arner, P (1999) Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects. Journal of Lipid Research 40, 2059–2065.CrossRefGoogle ScholarPubMed
Lee, JH, Reed, DR, Li, W-D, Xu, W, Joo, E-J, Kilker, RL, Nanthakumar, E, North, M, Sakul, H, Bell, C & Price, RA (1999) Genome scan for human obesity and linkage to markers in 20q13. American Journal of Human Genetics 64, 196–209.CrossRefGoogle ScholarPubMed
Lembertas, AV, Pérusse, L, Chagnon, YC, Fisler, JS, Warden, CH, Purcell-Huynh, DA, Dionne, FT, Gagnon, J, Nadeua, A, Lusis, AJ & Bouchard, C (1997) Identification of an obesity quantitative trait locus on mouse chromosome 2 and evidence of linkage to body fat and insulin on the human homologous region 20q. Journal of Clinical Investigation 100, 1240–1247.CrossRefGoogle ScholarPubMed
Lowell, BB & Fliers, JS (1997) Brown adipose tissue, beta3-adrenergic receptor and obesity. Annual Review of Medicine 48, 307–316.CrossRefGoogle Scholar
Magré, J, Laurell, H, Fizames, C, Antoine, PJ, Dib, C, Vigouroux, C, Bourut, C, Capeau, J, Weissenbach, J & Langin, D (1998) Genetic mapping, identification of a new dinucleotide repeat, and association with obesity and NIDDM. Diabetes 47, 284–286.CrossRefGoogle ScholarPubMed
Meirhaeghe, A, Helbecque, N, Cottel, D & Amouyel, P (1999) β2-adrenoceptor gene polymorphism, body weight and physical activity. Lancet 353, 896.CrossRefGoogle Scholar
Montague, CT, Faroogi, IS, Whitehead, JP, Soos, MA, Rau, H, Wareham, NJ, Sewter, CP, Digby, JE, Mohammed, SN, Hurst, JA, Cheetham, CH, Earley, AR, Barnett, AH, Prins, JB & O'Rahilly, S (1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387, 903–908.CrossRefGoogle ScholarPubMed
Mori, Y, Kim-Motoyama, H, Katakura, T, Yasuda, K, Kadowaki, H, Beamer, BA, Shuldiner, AR, Akanuma, Y, Yazaki, Y & Kadowaki, T (1998) Effect of the Pro12Ala variant of the human peroxisome proliferator-activated receptor γ-2 gene on adiposity, fat distribution and insulin sensitivity in Japanese men. Biochemical and Biophysical Research Communications 251, 195–198.CrossRefGoogle ScholarPubMed
Mori, Y, Kim-Motoyama, H, Ito, Y, Katakura, T, Yasuda, K, Ishiyama-Shigemoto, S, Yamada, K, Akanuma, Y, Ohashi, Y, Kimura, S, Yazaki, Y & Kadowaki, Y (1999) The Gln27Glu β2-adrenergic receptor variant is associated with obesity due to subcutaneous fat accumulation in Japanese men. Biochemical and Biophysical Research Communciations 258, 138–140.CrossRefGoogle ScholarPubMed
Norman, RA, Bogardus, C & Ravussin, E (1995) Linkage between obesity and a marker near the tum or necrosis factor-alpha locus in Pima Indians. Journal of Clinical Investigation 96, 158–162.CrossRefGoogle ScholarPubMed
Norman, RA, Tataranni, PA, Pratley, R, Thompson, DB, Hanson, RL, Prochazka, M, Baier, L, Ehm, MG, Sakul, H, Foroud, T, Garvey, WT, Burns, D, Knowler, WC, Bennett, PH, Bogardus, C & Ravussin, E (1998) Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians. American Journal of Human Genetics 62, 659–668.CrossRefGoogle ScholarPubMed
Norman, RA, Permana, P, Tanizawa, Y & Ravussin, E (1999) Absence of genetic variation in some obesity candidate genes (GLP1R, ASIP, MC4R, MC5R) among Pima Indians. International Journal of Obesity 23, 163–165.CrossRefGoogle Scholar
Oberkofler, H, Dallinger, G, Liu, YM, Hell, E, Krempler, F & Patcsh, W (1997) Uncoupling protein gene: quantification of expression levels in adipose tissue of obese and non-obese humans. Journal of Lipid Research 10, 2125–2133.CrossRefGoogle Scholar
Oppert, JM, Vohlm, C, Chagnon, M, Dionne, F, Cassard-Doulcier, AM, Ricquier, D, Perusse, L & Bouchard, C (1999) DNA polymorphism in the uncoupling protein (UCP) gene and human body fat. International Journal of Obesity 8, 526–531.Google Scholar
Otabe, S, Clement, K, Dubois, S, Lepretre, F, Pelloux, V, Leibel, R, Chung, W, Boutin, P, Guy-Grand, B, Frougel, P & Vasseur, F (1999) Mutation screening and association studies of the human uncoupling protein 3 gene in normoglycemic and diabetic morbidyly obese patients. Diabetes 48, 206–208.CrossRefGoogle ScholarPubMed
Pérusse, L, Chagnon, YC, Dionne, FT & Bouchard, C (1996) The human obesity gene map: the 1996 update. Obesity Research 5, 49–51.CrossRefGoogle Scholar
Pérusse, L, Chagnon, YC, Weisnagel, J & Bouchard, C (1999) The human obesity gene map: the 1998 update. Obesity Research 7, 111–129.CrossRefGoogle ScholarPubMed
Prins, JB, Nielser, CU, Winterford, CM, Bright, NA, Siddle, K, O'Rahilly, S, Walker, NI & Cameron, DP (1997) Tumor necrosis factor-alpha induces apoptosis of human adipose cells. Diabetes 46, 1939–1944.CrossRefGoogle ScholarPubMed
Ricquier, B (1999) Uncoupling protein-2 (UCP2): molecular and genetic studies. International Journal of Obesity 23, S38-S42.CrossRefGoogle Scholar
Ristow, M, Muller-Wieland, D, Pfeiffer, A, Krone, W & Kahn, CR (1998) Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. New England Journal of Medicine 339, 953–959.CrossRefGoogle Scholar
Rosenbaum, MD, Leibel, RL & Hirsch, MD (1997) Obesity. New England Journal of Medicine 337, 396–407.CrossRefGoogle ScholarPubMed
Rotimi, CN, Comuzzie, AG, Lowe, WL, Luke, A, Blangero, J & Cooper, RS (1999) The quantitative trait locus on chormosome 2 for serum leptin levels is confirmed in African-Americans. Diabetes 48, 643–276.CrossRefGoogle Scholar
Rutherford, S, Nyholt, DR, Curtain, RP, Quinan, SR, Gaffney, PT, Morris, BJ & Griffiths, LR (1997) Association of low density lipoprotein receptor microsatellite variant with obesity. International Journal Obesity 11, 1032–1037.CrossRefGoogle Scholar
Schoonjans, K, Maring, G, Staels, B & Auwerx, J (1997) Peroxisome proliferator-activated receptors, orphans with lgiands and function. Current Opinion in Lipidology 8, 159–166.CrossRefGoogle Scholar
Schrauwen, P, Walder, K & Ravussin, E (1999) Human uncoupling proteins and obesity. Obesity Research 7, 97–105.CrossRefGoogle ScholarPubMed
Sipiläinen, R, Uusitupa, M, Heikkinen, S, Rissanen, A & Laakso, M (1997) Polymorphism of the β3-adrenergic receptor gene affects basal metabolic rate in obese Finns. Diabetes 46, 77–80.CrossRefGoogle ScholarPubMed
Strobel, A, Issad, T, Camoin, L, Ozata, M & Strosberg, AD (1998) Leptin missense mutation association with hypogonadism and morbid obesity. Nature Genetics 18, 213–215.CrossRefGoogle ScholarPubMed
Strosberg, D (1997) Association of beta3-adrenoceptor polymorphism with obesity and diabetes: current status. Trends in Pharmacological Sciences 12, 449–454.CrossRefGoogle Scholar
Strosberg, D (1997) Structure and function of the beta3-adrenergic receptor. Annual Review of Pharmacology and Toxicolocy 37, 421–450.CrossRefGoogle Scholar
Umekawa, T, Yoshida, T, Sakane, N, Kogure, A, Kondo, M & Honjyo, H (1999) Trp64Arg mutation of β3-adrenocpetor gene deteriorates lipolysis induced by β3-adrenoceptor agonist in human omental adipocytes. Diabetes 48, 117–120.CrossRefGoogle ScholarPubMed
Vaisse, C, Clement, K, Guy-Grand, B & Frougel, P (1998) A framshift mutation in human MC4R is associated with a dominant form of obesity. Nature Genetics 20, 113–114.CrossRefGoogle Scholar
Valve, R, Heikkinen, S, Rissanen, A, Laakso, M & Uusitupa, M (1998) Synergistic effect of polymorphisms in uncoupling protein 1 and β3-adrenergic receptor genes on basal metabolic rate in obese Finns. Diabetologia 41, 357–361.CrossRefGoogle ScholarPubMed
Wacey, AL & Tuddenham, EGD (1998) Mutation databases on the web. Journal of Medical Genetics 35, 529–533.CrossRefGoogle ScholarPubMed
Warden, C (1999) Genetics of uncoupling proteins in humans. International Journal of Obesity 23, S46-S48.CrossRefGoogle ScholarPubMed
Willnow, TE (1999) The low-density lipoprotein receptor gene family: multiple roles in lipid metabolism. Journal of Molecular Medicine 77, 306–315.CrossRefGoogle ScholarPubMed
Wilson, AG, Symons, JA, McDowell, TL, McDevitt, HO & Duff, GW (1997) Effects of polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proceedings of the National Academy of Sciences, USA 7, 3194–3199.Google Scholar
Yeo, GSH, Faroogi, IS, Aminian, S, Halshall, DJ, Stanhope, RG & O'Rahilly, S (1999) A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nature Genetics 20, 111–112.CrossRefGoogle Scholar