Genetics of human obesity: Lessons from mouse models and candidate genes

Journal of Internal Medicine

Volumn 245, Issue 6, 1999, Pages 653-666

  Echwald, Soren M ^a,b  

^a STENO DIABETES CENTER   (Denmark)

^b HAGEDORN RESEARCH INSTITUTE   (Denmark)

Author keywords

Candidate genes; Genetics; Obesity

Indexed keywords

ANIMAL MODEL; CONFERENCE PAPER; FAMILY STUDY; GENE LOCATION; HUMAN; INHERITANCE; MOLECULAR CLONING; MOUSE; NONHUMAN; OBESITY; PATHOPHYSIOLOGY; PRIORITY JOURNAL; TWINS;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; MICE; MICE, INBRED STRAINS; OBESITY; PHENOTYPE; TWIN STUDIES;

EID: 0033064374     PISSN: 09546820     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2796.1999.00494.x     Document Type: Conference Paper

References (132)

1. 1 Pi-Sunyer FX. Health implications of obesity. Am J Clin Nutr 1991; 53: 1595S-1603.
2. 2 Anonymous Health implications of obesity. National Institutes of Health Consensus Development Conference Statement, National Institutes of Health Consensus Development Conference Consensus Statement 1985; 5: 1-7.
3. 3 Kral JG. Morbid obesity and related health risks. Ann Intern Med 1985; 103: 1043-7.
4. 4 McGinnis JM, Foege WH. Actual causes of death in the United States. JAMA 1993; 270: 2207-12.
5. 5 Lichtman SW, Pisarska K, Berman ER, Pestone M, Dowling H, Offenbacher E et al. Discrepancy between self-reported and actual caloric intake and exercise in obese subjects. N Engl J Med 1992; 327: 1893-8.
6. 6 Bandini LG, Schoeller DA, Cyr HN, Dietz WH. Validity of reported energy intake in obese und nonobese adolescents. Am J Clin Nutr 1990; 52: 421-5.
7. 7 DiPietro L, Anda RF, Williamson DF, Stunkard AJ. Depressive symptoms and weight change in a national cohort of adults. Int J Obesity 1992; 16: 745-53.
8. 8 Sobal J, Stunkard AJ. Socioeconomic status and obesity. Psychol Bull 1989; 105: 260-75.
9. 9 Dreniek EJ, Johnson D. Weight reduction by fasting and semistarvation in morbid obesity. Int J Obesity 1978; 2: 123-32.
10. 10 Sorensen TIA, Price RA. Secular trends in body mass index amongst Danish young men. Int J Obesity 1990; 14: 411-19.
11. 11 Kuczmarski RJ, Flegal KM, Campbell SM, Johnson CL. Increasing prevalence of overweight amongst US adults. The National Health Nutrition Examinalion Surveys 1960-91. JAMA 1994; 272: 205-11.
12. 12 Troiano RP, Flegal KM, Kuczmarski RJ, Campbell SM, Johnson CL. Overweight prevalence and trends for children and adolescents. The National Health Nutrition Examination Surveys 1963-91. Arch Pediatr Adolesc Med 1995; 149: 1085-91.
13. 13 Karlin S, Williams PT, Jensen S, Farquhar JW. Genetic analysis of the Stanford LRC family study data. I. Structured exploratory data analysis of height and weight measurements. Am J Epidmiol 1981; 113: 307-24.
14. 14 Borecki IB, Bonney GE, Rice T, Bouchard C, Rao DC. Influence of genotype-dependeny effects of covariates on the outcome of segregation analysis of the body mass index. Am J Human Genetics 1993; 53: 676-87.
15. 15 Lecomte E, Herbeth B, Nicaud V, Rakotovao R, Artur Y, Tiret L. Segregation analysis of fat mass and fat-free mass with age-dependent and sex-dependent effects - the Stanislaz family study. Gen Epidemiol 1997; 14: 51-62.
16. 16 Tiret L, Andre JL, Ducimetiere P, Herbeth B, Rakotovao R, Guegen R et al. Segregation analysis of height-adjusted weight with generation- and age-dependent effects. Gen Epidemiol 1992; 9: 389-403.
17. 17 Borecki IB, Rice T. Perusse L, Bouchard C, Rao DC. Major gene influence on the propensity to store fat in trunk versus extremity depots - evidence from the Quebec family study. Obes Research 1995; 3: 1-8.
18. 18 Zonta LA, Jayakar SD, Bosisio M, Galante A, Pennetti V. Genetic analysts of human obesity in an Italian sample. Human Heredity 1987; 37: 129-39.
19. 19 Byard PJ, Siervogel RM, Roche AF. Sibling correlations for weight/stature and calf circumference Human Biol 1983; 55: 677-85.
20. 20 Nirmala A, Mitchell LE, Rice T, Reddy PC, Rao DC. Assessment of adiposity in an Indian population: familial correlations. Gen Epidemiol 1993; 10: 133-43.
21. 21 Heller R, Garrison RJ, Havlik RJ, Feinleib M, Padgett S. Family resemblances in height and relative weight in the Framingham Heart Study. Int J Obesity 1984; 8: 399-405.
22. 22 Friedlander Y, Kark JD, Kaufmann NA, Berry EM, Stein Y. Familial aggregation of body mass index in ethnically diverse famlies in Jerusalem. The Jerusalem Lipid Research Clinic. Int J Obesity 1988; 12: 237-47.
23. 23 Bouchard C, Rice T, Lemieux S, Despres JP, Perusse L, Rao DC. Major gene for abdominal visceral fat area in the Quebec Family Study. Int J Obesity 1996; 20: 420-27.
24. 24 Rice T, Borecki JB. Bouchard C, Rao DC. Segregation analysis of fat mass and other body-composition measures derived from underwater weighing. Am J Human Gen 1993; 52: 967-73.
25. 25 Hasstedt SJ, Ramirez ME, Kuida H, Williams RR. Recessive inheritance of a relative fat pattern. Am J Human Gen 1989; 45: 917-25.
26. 26 Comuzzie AG, Blangero J, Mahaney MC, Mitchell BD, Hixson JE. Samollow PB et al. Major gene with sex-specific effects influences fat mass in Mexican Americans. Gen Epidemiol 1995; 12: 475-88.
27. 27 Price RA, Ness R, Laskarzcwski P. Common major gene inheritance of extreme overweight. Human Biol 1990; 62: 747-65.
28. 28 Moll PP, Burns TL, Lauer RM. The genetic and environmental sources of body mass index variability. Am J Human Gen 1991; 49: 1234-55.
29. 29 Sorensen TIA, Sonne-Holm S. Risk in childhood of development of severe adult obesity: Retrospective population-based case-cohort study. Am J Epidemiol 1988; 127: 104-13.
30. 30 Carey DG, Nguyen TV, Campbell LV, Chisholm DJ, Kelly P. Genetic influences on central abdominal fat: a twin study. Int J Obesity 1996; 20: 722-6.
31. 31 Bouchard C, Perusse L, Leblanc C, Tremblay A, Theriault G. Inheritance of the amount and distribution of human body fat. Int J Obesity 1988; 12: 212-15.
32. 32 Korkeila M, Kaprio J, Rissanen A, Koskenvuo M. Effects of gender and age on the heritability of body mass index. Int J Obesity 1991; 15: 647-54.
33. 33 Korkeila M, Kaprio J, Rissanen A, Koskenvuo M. Consistency and change of body mass index and weight. A study on 5967 adult Finnish twin pairs. Int J Obesity 1995; 19: 510-17.
34. 34 Herskind AM, McGue M, Sørensen TIA, Harvald B. Sex and age specific assessment of genetic and environmental influences on body mass index in twins. Int J Obesity 1996; 20: 106-13.
35. 35 Allison DB, Heshka S, Neale MC, Lykken DT, Heymsfield SB. A genetic analysts of relative weight amongst 4,020 twin pairs with an emphasis on sex effects. Health Psychol 1994; 13: 362-5.
36. 36 Carmichael CM, McGue M. A cross-sectional examination of height, weight and body mass index in adult twins. J Gerontol Series A - Biolog Sciences Med Sciences 1995; 50: B237-44.
37. 37 Fabsitz RR, Sholinsky P, Carmelli D. Genetic influences on adult weight-gain and maximum body mass index in male twins. Am J Epidemiol 1994; 140: 711-20.
38. 38 Bouchard C, Tremblay A, Despres JP, Nadeau A, Lupien PJ, Theriault G et al. The response to long-term overfeeding in identical twins. N Engl J Med 1990; 322: 1477-82.
39. 39 Bouchard C, Savard R, Despres JP, Tremblay A, Leblanc C. Body composition in adopted and biological siblings. Human Biol 1985; 57: 61-75.
40. 40 Allison DB, Kaprio J, Korkeila M, Koskenvuo M, Neale MC, Hayakawa K. The heritability of body-mass index amongst an international sample of monozygotic twins reared apart. Int J Obesity 1996; 20: 501-6.
41. 41 Stunkard AJ, Sørensen TIA, Hanis C. Teasdale TW, Chakraborty R, Schull WJ et al. An adoption study of human obesity. N Engl J Med 1986: 314: 193-8.
42. 42 Price RA, Cadoret RJ, Stunkard AJ, Troughton E. Genetic contributions to human fatness. Am J Psychiatry 1987; 144: 1003-8.
43. 41 Sorensen TIA, Price RA, Stunkard AJ, Sehulsinger F. Genetics of obesity in adult adoptees and their biological siblings. Br Med J 1989; 298: 87-90.
44. 44 Sorensen TIA, Stunkard AJ. Does obesity run in families because of genes? An adoption study using silhouettes as a measure of obesity. Acta Psychiatr Scand (Supplementum) 1996; 370: 67-72.
45. 45 Sorensen TIA, Holst C, Stunkard AJ. Childhood body mass index - genetic and familial environmental influences assessed in a longitudinal adoption study. Int J Obesity 1992; 16: 705-14.
46. 46 Vogler GP, Sorensen TIA, Stunkard AJ, Srinivasan MR, Rao DC. Influences of genes and shared family environment on adult body mass index assessed in an adoption study by a comprehensive path model. Int J Obesity 1995; 19: 40-45.
47. 47 Dragani TA, Zeng ZB, Canzian F, Gariboldi M, Ghilarducci MT, Manenti G et al. Mapping of body-weight loci on mouse chromosome-X. Mammalian Genome 1995; 6: 778-81.
48. 48 Price RA, Gottesman II. Body fat in identical twins reared apart. Behav Gen 1991; 21: 1-7.
49. 49 Warden CH, Fisler JS, Shoemaker SM, Wen PZ, Svenson KL, Pace MJ et al. Identification of 4 chromosomal loci determining obesity in a multifactorial mouse model. J Clin Invest 1995; 95: 1545-52.
50. 50 Frankel WN, Valenzuela A, Lutz CM, Johnson FW, Dietrich WF, Coffin JM. New seizure frequency QTL and the complex genetics of epilepsy in el mice. Mammalian Genome 1995; 6: 830-38.
51. 51 Tanksley SD. Mapping polygenes. Ann Rev Gen 1993; 27: 205-33.
52. 52 Mackay TF. The nature of quantitative genetic variation revisited: lessons from Drosophila bristles. Bioessays 1996; 18: 113-21.
53. 53 Shrimpton AE, Robertson A. The isolation of polygenic factors controlling bristle score in Drosophila melanogaster, 2. Distribution of third chromosome bristle effects within chomosome sections. Genetics 1988; 118: 445-59.
54. 54 Perusse L, Chagnon YC, Dionne FT. Bouchard C. The human obesity gene map. The 1996 update. Obesity Research 1997; 5: 49-61.
55. 55 Frankham R. The nature of quantitative genetic variation in Drosophila, II. Average dominance of abdominal bristle polygenes. Aust J Biol Sciences 1974; 27: 683-6.
56. 56 Spickett SG, Thoday JM. Regular responses to selection. 3. Interaction between located polygenes. Genet Research 1966; 7: 96-121.
57. 57 Clausen JO, Borch-Johnsen K, Ibsen H, Bergman RN, Hougaard P, Winther K et al. Insulin sensitivity index, acute insulin response and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender body fat, physical fitness and life-style factors. J Clin Invent 1996; 98: 1195-209.
58. 58 Galli J. Li LS, Glaser A, Ostenson CG, Jiao H, Fakhrai-Rad H et al. Genetic analysis of non-insulin-dependent diabetes mellitus in the GK rat. Nature Gen 1996; 12: 31-7.
59. 59 Gauguier D, Froguel P, Parent V, Bernard C, Bihoreau MT, Portha B et al. Chromosomal mapping of genetic loci associated with non-insulin-dependent diabetes in the GK rat. Nature Gen 1996; 12: 39-43.
60. 60 Wang W, Okayama H, Shirato K. Genotypes of cystic fibrosis (CF) reported in the world find polymorphisms of cystic fibrosis transmembrane conductance regulator (CFTR) gene in Japanese. Nippan Rinsho Japanese J Clin Med 1996; 54: 525-32.
61. 61 Price RA, Charles MA, Pellitt DJ, Knowler WC. Obesity in Pima Indians: large increases amongst post-World War II birth cohorts. Am J Phys Anthrop 1993; 92: 473-9.
62. 62 Sicree RA, Zimmet PZ, King H, Coventry JS. Weight change amongst Nauruans over 65 years. Diabetes Research Clin Practice 1987; 3: 327-16.
63. 63 Reed DR, Ding Y, Xu W, Cather C, Price RA. Human obesity does not segregate with the chromosomal regions of Prader-Willi, Bardet-Biedl, Cohen, Borjeson or Wilson Turner syndromes. Int J Obesity 1995; 19: 599-603.
64. 64 Bray GA, York DA. Hypothnlamic and genetic obesity in experimental animals. Physiol Rev 1979; 59: 719-809.
65. 65 Coleman DL. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia 1973; 9: 294-8.
66. 66 Coleman DL, Hummel KP. Effects of parabiosis of normal with genetically diabetic mice. Am J Physiol 1969; 217: 1298-1304.
67. 67 Sørensen TIA, Echwald SM, Holm JC. Leptin in obesity. Br Med 1996; 313: 955-4.
68. 68 Bray GA. Leptin and leptinomania. Lancet 1996; 348: 140-41.
69. 69 Zhang YY, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homolog. Nature 1994; 372: 425-32.
70. 70 Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse ob protein - evidence for a peripheral signal linking adiposity and central neural networks. Science 1995; 269: 546-9.
71. 71 Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D et al. Weight-reducing effects of the plasma-protein encoded by the obese gene. Science 1995; 269: 543-6.
72. 72 Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T et al Effects of the obese gene-product on body-weight regulation in ob/ ob mice. Science 1995; 269: 540-43.
73. 73 Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR et al. Serum immunoreactive leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292-5.
74. 74 Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH et al. Decreased cerebrospinal-fluid/ serum leptin ratio in obesity - a possible mechanism for leptin resistance. Lancet 1996; 348: 159-61.
75. 75 Schwartz MW, Peskind H, Raskind M, Boyko EJ, Porte D. Cerebrospinal-fluid leptin levels - relationship to plasma-levels and to adiposity in humans. Nature Med 1996; 2: 589-93.
76. 76 Echwald SM, Sorensen TD, Sørensen TIA, Tybjærg-Hansen A, Andersen T, Chung WK et al. Amino acid variants in the human leptin receptor: lack of association to juvenile onset obesity. Biochem Biophys Research Comm 1997; 233: 248-52.
77. 77 Chung WK, Powerkehoe L, Chua M, Chu F, Aronne L, Huma Z et al. Exonic and intronic sequence variation in the human leptin receptor (LEPR). Diabetes 1997; 46: 1509-11.
78. 78 Thompson DB, Ravussin E, Bennett PH, Bogardus C. Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians. Human Molec Gen 1997; 6: 675-9.
79. 79 Gotoda T, Manning BS, Goldstone AP, Imrie H, Evans AL, Strosberg AD et al. Leptin receptor gene variation and obesity - lack of association in a white British male-population. Human Molec Gen 1997; 6: 869-76.
80. 80 Thompson DR, Norman RA, Ravussin E, Knowler WC, Bennen P, Bogardus C. Association of the gln223arg polymorphism in the leptin receptor gene with plasma leptin levels insulin-secretion and NIDDM in Pima-Indians. Diabetes 1997; 46: 960.
81. 81 Echivald SM, Rasmussen SB, Sorensen TIA, Andersen T, Tybjærg-Hansen A, Clausen JO et al. Identification of two novel missense mutations in the human OB gene. Int J Obesity 1997.
82. 82 Considine RV, Considine EL, Williams CJ, Nyce MR, Zhang P, Opentanova I et al. Mutation screening and identification of a sequence variation in the human ob gene coding region. Biochem Biophys Research Comm 1996; 220: 735-9.
83. 83 Clement K, Garner C, Hager J. Philippi A, Leduc C, Carey A et al. Indication for linkage of the human ob gene region with extreme obesity. Diabetes 1996; 45: 687-90.
84. 84 Reed DR, Ding Y, Xu WZ, Gather C, Green ED, Price RA. Extreme obesity may be linked to markers flanking the human ob gene. Diabetes 1996; 45: 691-4.
85. 85 Duggirala R, Stern MP, Mitchell BD, Reinhart LJ. Shipman PA, Uresandi OC et al. Quantitative variation in obesity-related traits and insulin precursors linked to the ob gene region on human-chromosome-7. Am J Human Gen 1996; 59: 694-703.
86. 86 Borecki IB, Rice T, Perusse L, Bouchard C, Rao DC. An exploratory investigation of genetic linkage with body composition and fatness phenotypes: the Quebec family study. Obesity Research 1994; 2: 213-19.
87. 87 Montague CT, Farooqi IS, Whitebead JP, Soos MA, Rau H, Wareham NJ et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387: 903-8.
88. 88 Michaud EJ, Bultman SJ, Klebig ML, Vanvugt MJ, Stubbs LJ, Russell LB et al. A molecular-model for the genetic and phenotypic characteristics of the mouse lethal yellow (a (y)) mutation. Proceedings of the National Academy of Sciences of the United States of America 1994; 91: 2562-6.
89. 89 Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997; 88: 131-41.
90. 90 Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 1997; 385: 165-8.
91. 91 Nobentrauth K, Naggert JK, North MA, Nishina PM. A candidate gene for the mouse mutation tubby. Nature 1996; 380: 534-8.
92. 92 Tartaglia LA, Dembski M, Weng X, Deng NH, Culpepper J, Devos R et al. Identification and expression cloning of a leptin receptor ob-R. Cell 1995; 83: 1263-71.
93. 93 Chua SC, Chung WK, Wupeng XS, Zhang YY, Liu SM, Tartaglia L et al. Phenotypes of mouse diabetes and rat fatty due to mutations in the ob (leptin) receptor. Science 1996; 271: 994-6.
94. 94 Bultman SJ, Michaud EJ, Woychik RP. Molecular characterization of the mouse agouti locus. Cell 1992; 71: 1195-1204.
95. 95 Kleyn PW, Fan W, Kovats SG, Lee JJ, Pulido JC, Wu Y et al. Identification and characterization of the mouse obesity gene tubby - a member of a novel gene family. Cell 1996; 85: 281-90.
96. 96 Naggert JK, Fricker LD, Varlamov O, Nishina PM, Rouille Y, Steiner DF et al. Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase-e mutation which reduces enzyme-activity. Nature Gen 1995; 10: 135-42.
97. 97 Takaya K, Ogawa Y, Hiraoka J, Hosoda K, Yamori Y, Nakao K et al. Nonsense mutation of leptin receptor in the obese spontaneously hypertensive koletsky rat. Nature Gen 1996; 14: 130-31.
98. 98 Lee GH, Li C, Montez J, Halaas J, Darvishzadeh J, Friedman JM. Leptin receptor mutations in 129 db (3j) /db (3j) mice and nih fa (cp) /fa (cp) rats. Mammalian Genome 1997; 8: 445-7.
99. 99 Jacobsson A, Stadler U, Glotzer MA, Kozak LP. Mitochondrial uncoupling protein from mouse brown fat. Molecular cloning genetic mapping and mRNA expression. J Biol Chem 1985; 260: 16250-54.
100. 100 Silva JE, Rabelo R. Regulation of the uncoupling protein gene-expression. Eur J Endocrinol 1997; 136: 251-64.
101. 101 Enerback S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, Harper ME et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 1997; 387: 90-94.
102. 102 Kopecky J, Clarke G, Enerback S. Spiegelman B, Kozack LP. Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity. J Clin Invest 1995; 96: 2914-23.
103. 103 Lowell BBS, Ssusulic V, Hamann A, Lawitts JA, Himms-Hagen J, Boyer BB et al. Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 1993; 366: 740-42.
104. 104 Urhammer SA, Fridberg M, Sorensen TIA, Echwald SM, Andersen T, Tybjæg-Hansen A et al. Studies of genetic variability of the uncoupling protein 1 gene in Caucasian subjects with juvenile-onset obesity. J Clin Endocrinal Metabol 1997; 82: 4069-74.
105. 105 Oppert JM, Vohl MC, Chagnon M, Dionne FT, Cassarddoulcier AM, Ricquier D et al. DNA polymorphism in the uncoupling protein (UCP) gene and human-body fat. Int J Obesity 1994; 18: 526-31.
106. 106 Taylor BA, Phillips SJ. Detection of obesity QTLs on mouse chromosome-1 and chromosome-7 by selective DNA pooling, Genomics 1996; 34: 389-98.
107. 107 Møller AM, Hansen T, Almind K, Hansen L, Echwald SM, Clausen JO et al. Decreased insulin-secretion in healthy subjects with sequence variants in the sulfonylurca receptor gene. Diabetologia 1996; 39: 11.
108. 108 Hansen T, Echwald SM, Hansen L, Møller AM, Almind K, Clausen JO et al. Decreased tolbutamide-stimuluted secretion in healthy subjects with sequence variants in the high affinity sulfonylurea receptor gene. Diabetes 1997; 47: 598-605.
109. 109 Hani E, Clement K, Velho G, Vionnet N, Hager J, Philippi A et al. Genetic-studies of the sulfonylurea receptor gene locus in NIDDM and in morbid obesity amongst French Caucasians. Diabetes 1997; 46: 688-94.
110. 110 Gimeno RE, Dembski M, Weng X, Deng NH, Shyjan AW, Gimeno CJ et al. Cloning and characterization of an uncoupling protein homolog - a potential molecular mediator of human thermogenesis. Diabetes 1997; 46: 900-906.
111. 111 Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, Levimcyrucis C et al. Uncoupling protein-2 - a novel gene linked to obesity and hyperinsulinemia. Nature Gen 1997; 15: 269-72.
112. 112 Urhammer SA, Dalgaard LT, Sorensen TIA, Møller AM, Andersen T, Tybjærg-Hansen A et al. Mutational analysis of the coding region of the uncoupling protein 2 gene in obese NIDDM patients: Studies of the impact of a common amino acid polymorphism on juvenile and maturity onset forms of obesity and insulin resistance. Diabetologia 1997; 40: 1227-30.
113. 113 Bouchard C, Perusse L, Chagnon YC, Warden C, Ricquier D. Linkage between markers in the vicinity of the uncoupling protein-2 gene and resting metabolic rate in humans. Human Molec Gen 1997; 6: 1887-9.
114. 114 Boss O, Samec S, Paolonigiacobino A, Rossier C, Dulloo A, Seydoux J et al. Uncoupling protein-3 - a new member of the mitochondrial carrier family with tissue-specific expression. FEBS Letters 1997: 408: 39-42.
115. 115 Lowell BB, Ssusulic V, Hamand A, Lawitts JA. Himmshagen J, Boyer BB et al. Development of obesity in transgenic mice after genetic ablation of brown adipose-tissue. Nature 1993; 366: 740-42.
116. 116 Tataranni PA, Shuldiner AR, Ravussin E. Lipid-metabolism and the Trp64Arg beta (3) -adrenergic receptor mutation in Pima-Indians. Diabetes 1996; 45: 328.
117. 117 Fujisawa T, Ikegami H, Yamato M. Takekawa K, Nakagawa Y, Hamada Y et al. Association of Trp64Arg mutation of the beta-3-adrenergic-receptor with NIDDM and body-weight gain. Diabetologia 1996; 39: 349-52.
118. 118 Clement K, Vaisse C, Manning BS, Basdevant A, Guygrand B, Ruiz J et al. Genetic-variation in the beta (3) -adrenergic receptor and an increased capacity to gain weight in patients with morbid-obesity. N Engl J Med 1995; 333: 352-4.
119. 119 Widen E, Lehto M, Kanninen T, Walston J, Shuldiner AR, Groop LC. Association of a polymorphism in the beta (3) -adrenergic-receptor gene with features of the insulin-resistance syndrome in Finns. N Engl J Med 1995; 333: 348-51.
120. 120 Walston J, Silver K, Bogardus C, Knowler WC, Cell FS, Austin S et al. Time of onset of non-insulin-dependent diabetes-mellitus and genetic-variation in the beta (3) -adrenergic-receptor gene. N Engl J Med 1995; 333: 343-7.
121. 121 Kurabayashi T, Carey DGP, Morrison NA. The beta-3-adrenergic receptor gene Trp64Arg mutation is overrepresented in obese women - effects on weight, BMI, abdominal fat, blood-pressure and reproductive history in an elderly Australian population. Diabetes 1996; 45: 1358-63.
122. 122 Yoshioka K, Yoshida T, Sakane N, Umekawa T, Takahashi T, Sakai Y et al. Association of Trp64Arg mutation of the beta-3-adrenergic receptor gene with NIDDM current and maximal body-mass index. Diabetologia 1996; 39: 1410.
123. 123 Sipilainen R, Uusitupa M, Heikkinen S, Rissanen A, Laakso M. Polymorphism of the beta (3) -adrenergic receptor gene affects basal metabolic-rate in obese Finns. Diabetes 1997; 46: 77-80.
124. 124 Kimmotoyama H, Yasuda K, Yamaguchi T, Yamada N, Katakura T, Shuldiner AR et al. A mutation of the beta-3-adrenergic receptor is associated with visceral obesity but decreased serum triglyceride. Diabetologia 1997; 40: 469-72.
125. 125 Li LS, Lönnqvist F, Luthman H, Arner P. Phenotypic characterization of the Trph4Arg polymorphism in the beta (3) -adrenergic receptor gene in normal-weight and obese subjects. Diabetologia 1996; 39: 857-60.
126. 126 Gagnon J, Mauriege P. Roy S, Sjostrom D, Chagnon YC, Dionne FT et al. The Trp64Arg mutation of the beta-3 adrenergic-receptor gene has no effect on obesity phenotypes in the Quebec family study and Swedish obese subjects cohorts. J Clin Invest 1996; 98: 2086-93.
127. 127 Silver K, Walston J, Wang YH, Dowse G, Zimmet P, Shuldiner AR. Molecular scanning for mutations in the beta (3) -adrenergic receptor gene in Nauruans with obesity and non-insulin-dependent diabetes-mellitus. J Clin Endocrinol Metabol 1996; 81: 4155-8.
128. 128 Fujisawa T, Ikegami H, Yamato E, Hamada Y, Kamide K, Rakugi H et al. Trp64Arg mutation of beta-3-adrenergic receptor in essential-hypertension - insulin-resistance and the adrenergic system. Am J Hypertens 1997; 10: 101-5.
129. 129 Ueda K, Tanizawa Y, Oota Y, Inoue H. Kizuki N, Tsukuda K et al. Prevalence of the Trp64Arg missense mutation of the beta (3) -adrenergic receptor gene in Japanese subjects. Metab Clin Exper 1997; 46: 199-202.
130. 130 Hinney A, Lentes KU, Rosenkranz K, Barth N, Roth H, Ziegler A et al. Beta (3) -adrenergic-receptor allele distributions in children, adolescents and young-adults with obesity underweight or anorexia nervosa. Int J Obesity 1997; 21: 224-30.
131. 131 Snitker S, Odeleye OE, Hellmer J, Boschmann M, Monroe MB, Shuldiner AR. No effect of the Trp64Arg beta (3) -adrenoceptor variant on in-vivo lipolysis in subcutaneous adipose-tissue. Diabetologia 1997; 40; 838-42.
132. 132 Urhammer SA, Clausen JO, Hansen T, Pedersen O. Insulin sensitivity and body weight changes in young white carriers of the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor gene. Diabetes 1996; 45: 1115-20.