FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 333:352-354 August 10, 1995 Number 6 Next

	Full Text PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background The ₃-adrenergic receptor, located mainly in adipose tissue, is involved in the regulation of lipolysis and thermogenesis. The potential relevance of this receptor to obesity in humans led us to screen obese French patients for a recently identified mutation in the gene for the receptor.

Methods We used the polymerase chain reaction to amplify a region of the gene for the ₃-adrenergic receptor encoding amino acid residues 27 to 110 in genomic DNA extracted from leukocytes from 185 patients with morbid obesity (body-mass index [the weight in kilograms divided by the square of the height in meters], >40) and 94 normal subjects. A mutation resulting in the replacement of tryptophan by arginine at position 64 (Trp64Arg) was detected by an analysis of restriction-fragment–length polymorphisms with the use of the endonuclease Bst NI, which discriminates between the normal and mutant sequences.

Results The frequency of the Trp64Arg allele was similar in the morbidly obese patients and the normal subjects (0.08 and 0.10, respectively). However, the patients with morbid obesity who were heterozygous for the Trp64Arg mutation had an increased capacity to gain weight; the mean weight in the 14 heterozygous patients was 140 kg, as compared with 126 kg in the 171 patients without the mutation (P = 0.03). There were no homozygotes in this sample. The cumulative 25-year change in weight (from the age of 20 years) was 67 kg in the Trp64Arg heterozygotes, as compared with 51 kg in those without the mutation. The maximal weight differential (the maximal lifetime weight minus the weight at 20 years of age) in the Trp64Arg heterozygotes was 74 kg, as compared with 59 kg in the patients without the mutation (P = 0.02).

Conclusions People with the Trp64Arg mutation of the gene for the ₃-adrenergic receptor may have an increased capacity to gain weight.

Source Information

From the Centre National de la Recherche Scientifique, Unité CNRS-EP10, Institut Pasteur and University Hospital, Lille, France (K.C., C.V., J.R., P.F.); the Département de Nutrition, Hôpital Hôtel Dieu, Paris (K.C., A.B., B.G.-G.); the Institut Cochin de Génétique Moléculaire, Laboratoire d'Immunopharmacologie Moléculaire, Unité CNRS-UPR-0415, Paris (B.S.J.M., A.D.S.); and the Department of Medicine, Johns Hopkins University School of Medicine, Baltimore (K.D.S., A.R.S.).

Address reprint requests to Dr. Froguel at CNRS-EP10, Institut Pasteur, 1 Rue Calmette, B.P. 245, 59019 Lille CEDEX, France.

Full Text of this Article

This article has been cited by other articles:

• Ortega-Alonso, A, Sipila, S, Kujala, U M, Kaprio, J, Rantanen, T (2009). Genetic influences on adult body mass index followed over 29 years and their effects on late-life mobility: a study of twin sisters. J. Epidemiol. Community Health 63: 651-658 [Abstract] [Full Text]  
• Pierola, J., Barcelo, A., de la Pena, M., Barbe, F., Soriano, J. B., Sanchez Armengol, A., Martinez, C., Agusti, A. (2007). {beta}3-Adrenergic receptor Trp64Arg polymorphism and increased body mass index in sleep apnoea. Eur Respir J 30: 743-747 [Abstract] [Full Text]  
• Cecil, J. E, Palmer, C. N., Fischer, B., Watt, P., Wallis, D. J, Murrie, I., Hetherington, M. M (2007). Variants of the peroxisome proliferator-activated receptor {gamma}- and {beta}-adrenergic receptor genes are associated with measures of compensatory eating behaviors in young children. Am. J. Clin. Nutr. 86: 167-173 [Abstract] [Full Text]  
• Beuther, D. A., Weiss, S. T., Sutherland, E. R. (2006). Obesity and Asthma. Am. J. Respir. Crit. Care Med. 174: 112-119 [Abstract] [Full Text]  
• Masuo, K., Katsuya, T., Fu, Y., Rakugi, H., Ogihara, T., Tuck, M. L. (2005). Lys418Asn Polymorphism of the {alpha}2-Adrenoceptor Gene Relates to Serum Uric Acid Levels But Not to Insulin Sensitivity. Hypertension 46: 144-150 [Abstract] [Full Text]  
• Masuo, K., Katsuya, T., Fu, Y., Rakugi, H., Ogihara, T., Tuck, M. L. (2005). {beta}2- and {beta}3-Adrenergic Receptor Polymorphisms Are Related to the Onset of Weight Gain and Blood Pressure Elevation Over 5 Years. Circulation 111: 3429-3434 [Abstract] [Full Text]  
• Romieu, I., Lazcano-Ponce, E., Sanchez-Zamorano, L. M., Willett, W., Hernandez-Avila, M. (2004). Carbohydrates and the Risk of Breast Cancer among Mexican Women. Cancer Epidemiol. Biomarkers Prev. 13: 1283-1289 [Abstract] [Full Text]  
• Eberle, D., Clement, K., Meyre, D., Sahbatou, M., Vaxillaire, M., Le Gall, A., Ferre, P., Basdevant, A., Froguel, P., Foufelle, F. (2004). SREBF-1 Gene Polymorphisms Are Associated With Obesity and Type 2 Diabetes in French Obese and Diabetic Cohorts. Diabetes 53: 2153-2157 [Abstract] [Full Text]  
• Matsushita, Y., Yokoyama, T., Yoshiike, N., Matsumura, Y., Date, C., Kawahara, K., Tanaka, H. (2003). The Trp64Arg Polymorphism of the {beta}3-Adrenergic Receptor Gene Is Not Associated with Body Weight or Body Mass Index in Japanese: A Longitudinal Analysis. J. Clin. Endocrinol. Metab. 88: 5914-5920 [Abstract] [Full Text]  
• Suzuki, N., Matsunaga, T., Nagasumi, K., Yamamura, T., Shihara, N., Moritani, T., Ue, H., Fukushima, M., Tamon, A., Seino, Y., Tsuda, K., Yasuda, K. (2003). {alpha}2B-Adrenergic Receptor Deletion Polymorphism Associates with Autonomic Nervous System Activity in Young Healthy Japanese. J. Clin. Endocrinol. Metab. 88: 1184-1187 [Abstract] [Full Text]  
• Froguel, P., Boutin, P. (2001). Genetics of Pathways Regulating Body Weight in the Development of Obesity in Humans. Exp. Biol. Med. 226: 991-996 [Abstract] [Full Text]  
• Oizumi, T., Daimon, M., Saitoh, T., Kameda, W., Yamaguchi, H., Ohnuma, H., Igarashi, M., Eguchi, H., Manaka, H., Tominaga, M., Kato, T. (2001). Genotype Arg/Arg, but not Trp/Arg, of the Trp64Arg Polymorphism of the {beta}3-Adrenergic Receptor Is Associated With Type 2 Diabetes and Obesity in a Large Japanese Sample. Diabetes Care 24: 1579-1583 [Abstract] [Full Text]  
• Guimaraes, S., Moura, D. (2001). Vascular Adrenoceptors: An Update. Pharmacol. Rev. 53: 319-356 [Abstract] [Full Text]  
• Susulic, V. S., LaVallette, L., Duzic, E., Chen, L., Shuey, D., Karathanasis, S. K., Steiner, K. E. (2001). Expression of the Human {beta}3-Adrenergic Receptor Gene in SK-N-MC Cells Is Under the Control of a Distal Enhancer. Endocrinology 142: 1935-1949 [Abstract] [Full Text]  
• Schoeller, D. A (2001). The importance of clinical research: the role of thermogenesis in human obesity. Am. J. Clin. Nutr. 73: 511-516 [Abstract] [Full Text]  
• Sharma, A. M., Pischon, T., Hardt, S., Kunz, I., Luft, F. C. (2001). Hypothesis: {beta}-Adrenergic Receptor Blockers and Weight Gain : A Systematic Analysis. Hypertension 37: 250-254 [Abstract] [Full Text]  
• Dionne, I. J., Turner, A. N., Tchernof, A., Pollin, T. I., Avrithi, D., Gray, D., Shuldiner, A. R., Poehlman, E. T. (2001). Identification of an Interactive Effect of {beta}3- and {alpha}2b-Adrenoceptor Gene Polymorphisms on Fat Mass in Caucasian Women. Diabetes 50: 91-95 [Abstract] [Full Text]  
• Wajchenberg, B. L. (2000). Subcutaneous and Visceral Adipose Tissue: Their Relation to the Metabolic Syndrome. Endocr. Rev. 21: 697-738 [Abstract] [Full Text]  
• Walston, J., Silver, K., Hilfiker, H., Andersen, R. E., Seibert, M., Beamer, B., Roth, J., Poehlman, E., Shuldiner, A. R. (2000). Insulin Response to Glucose Is Lower in Individuals Homozygous for the Arg 64 Variant of the {beta}-3-Adrenergic Receptor. J. Clin. Endocrinol. Metab. 85: 4019-4022 [Abstract] [Full Text]  
• Urhammer, S. A., Hansen, T., Borch-Johnsen, K., Pedersen, O. (2000). Studies of the Synergistic Effect of the Trp/Arg64 Polymorphism of the {beta}3-Adrenergic Receptor Gene and the -3826 A->G Variant of the Uncoupling Protein-1 Gene on Features of Obesity and Insulin Resistance in a Population-Based Sample of 379 Young Danish Subjects. J. Clin. Endocrinol. Metab. 85: 3151-3154 [Abstract] [Full Text]  
• Devlin, M. J., Yanovski, S. Z., Wilson, G. T. (2000). Obesity: What Mental Health Professionals Need to Know. Am. J. Psychiatry 157: 854-866 [Abstract] [Full Text]  
• Hasegawa, Y., Fujii, K., Yamada, M., Igarashi, Y., Tachibana, K., Tanaka, T., Onigata, K., Nishi, Y., Kato, S., Hasegawa, T. (2000). Identification of Novel Human GH-1 Gene Polymorphisms that Are Associated with Growth Hormone Secretion and Height. J. Clin. Endocrinol. Metab. 85: 1290-1295 [Abstract] [Full Text]  
• Brodde, O.-E., Michel, M. C. (1999). Adrenergic and Muscarinic Receptors in the Human Heart. Pharmacol. Rev. 51: 651-690 [Abstract] [Full Text]  
• Carel, J. C., Le Stunff, C., Condamine, L., Mallet, E., Chaussain, J. L., Adnot, P., Garabédian, M., Bougnères, P. (1999). Resistance to the Lipolytic Action of Epinephrine: A New Feature of Protein Gs Deficiency. J. Clin. Endocrinol. Metab. 84: 4127-4131 [Abstract] [Full Text]  
• Dzimiri, N. (1999). Regulation of beta -Adrenoceptor Signaling in Cardiac Function and Disease. Pharmacol. Rev. 51: 465-502 [Abstract] [Full Text]  
• Barzilai, N., She, L., Liu, L., Wang, J., Hu, M., Vuguin, P., Rossetti, L. (1999). Decreased visceral adiposity accounts for leptin effect on hepatic but not peripheral insulin action. Am. J. Physiol. Endocrinol. Metab. 277: E291-E298 [Abstract] [Full Text]  
• Bogardus, S. T. Jr, Concato, J., Feinstein, A. R. (1999). Clinical Epidemiological Quality in Molecular Genetic Research: The Need for Methodological Standards. JAMA 281: 1919-1926 [Abstract] [Full Text]  
• Festa, A., Krugluger, W., Shnawa, N., Hopmeier, P., Haffner, S. M., Schernthaner, G. (1999). Trp64Arg Polymorphism of the {beta}3-Adrenergic Receptor Gene in Pregnancy: Association with Mild Gestational Diabetes Mellitus. J. Clin. Endocrinol. Metab. 84: 1695-1699 [Abstract] [Full Text]  
• Jequier, E., Tappy, L. (1999). Regulation of Body Weight in Humans. Physiol. Rev. 79: 451-480 [Abstract] [Full Text]  
• Fogelholm, M., Valve, R., Kukkonen-Harjula, K., Nenonen, A., Hakkarainen, V., Laakso, M., Uusitupa, M. (1998). Additive Effects of the Mutations in the {beta}3-Adrenergic Receptor and Uncoupling Protein-1 Genes on Weight Loss and Weight Maintenance in Finnish Women. J. Clin. Endocrinol. Metab. 83: 4246-4250 [Abstract] [Full Text]  
• GarcÍa-Rubi, E., Starling, R. D., Tchernof, A., Matthews, D. E., Walston, J. D., Shuldiner, A. R., Silver, K., Poehlman, E. T., Calles-Escandón, J. (1998). Trp64Arg Variant of the {beta}3-Adrenoceptor and Insulin Resistance in Obese Postmenopausal Women. J. Clin. Endocrinol. Metab. 83: 4002-4005 [Abstract] [Full Text]  
• Büettner, R., Schäffler, A., Arndt, H., Rogler, G., Nusser, J., Zietz, B., Enger, I., Hügl, S., Cuk, A., Schölmerich, J., Palitzsch, K.-D. (1998). The Trp64Arg Polymorphism of the {beta} 3-Adrenergic Receptor Gene Is Not Associated with Obesity or Type 2 Diabetes Mellitus in a Large Population-Based Caucasian Cohort. J. Clin. Endocrinol. Metab. 83: 2892-2897 [Abstract] [Full Text]  
• Fujisawa, T., Ikegami, H., Kawaguchi, Y., Ogihara, T. (1998). Meta-Analysis of the Association of Trp64Arg Polymorphism of {beta}3-Adrenergic Receptor Gene with Body Mass Index. J. Clin. Endocrinol. Metab. 83: 2441-2444 [Abstract] [Full Text]  
• Jockers, R., Issad, T., Zilberfarb, V., de Coppet, P., Marullo, S., Strosberg, A. D. (1998). Desensitization of the {beta}-Adrenergic Response in Human Brown Adipocytes. Endocrinology 139: 2676-2684 [Abstract] [Full Text]  
• Knott, S. A., Marklund, L., Haley, C. S., Andersson, K., Davies, W., Ellegren, H., Fredholm, M., Hansson, I., Hoyheim, B., Lundstrom, K., Moller, M., Andersson, L. (1998). Multiple Marker Mapping of Quantitative Trait Loci in a Cross Between Outbred Wild Boar and Large White Pigs. Genetics 149: 1069-1080 [Abstract] [Full Text]  
• Esterbauer, H., Oberkofler, H., Liu, Y.-M., Breban, D., Hell, E., Krempler, F., Patsch, W. (1998). Uncoupling protein-1 mRNA expression in obese human subjects: the role of sequence variations at the uncoupling protein-1 gene locus. J. Lipid Res. 39: 834-844 [Abstract] [Full Text]  
• Rosenbaum, M., Leibel, R. L. (1998). The Physiology of Body Weight Regulation: Relevance to the Etiology of Obesity in Children. Pediatrics 101: 525-539 [Abstract] [Full Text]  
• Elbein, S. C. (1997). The Genetics of Human Noninsulin-Dependent (Type 2) Diabetes Mellitus. J. Nutr. 127: 1891-1891 [Abstract] [Full Text]  
• Fisler, J. S., Warden, C. H. (1997). Mapping of Mouse Obesity Genes: A Generic Approach to a Complex Trait. J. Nutr. 127: 1909-1909 [Abstract] [Full Text]  
• Nagase, T., Aoki, A., Yamamoto, M., Yasuda, H., Kado, S., Nishikawa, M., Kugai, N., Akatsu, T., Nagata, N. (1997). Lack of Association between the Trp64Arg Mutation in the {beta}3-Adrenergic Receptor Gene and Obesity in Japanese Men: A Longitudinal Analysis. J. Clin. Endocrinol. Metab. 82: 1284-1287 [Abstract] [Full Text]  
• Zilberfarb, V, Pietri-Rouxel, F, Jockers, R, Krief, S, Delouis, C, Issad, T, Strosberg, A. (1997). Human immortalized brown adipocytes express functional beta3-adrenoceptor coupled to lipolysis. J. Cell Sci. 110: 801-807 [Abstract]  
• Soloveva, V., Graves, R. A., Rasenick, M. M., Spiegelman, B. M., Ross, S. R. (1997). Transgenic Mice Overexpressing the {beta}1-Adrenergic Receptor in Adipose Tissue Are Resistant to Obesity. Mol. Endocrinol. 11: 27-38 [Abstract] [Full Text]  
• Insel, P. A. (1996). Adrenergic Receptors -- Evolving Concepts and Clinical Implications. NEJM 334: 580-585 [Full Text]  
• Susulic, V. S., Frederich, R. C., Lawitts, J., Tozzo, E., Kahn, B. B., Harper, M.-E., Himms-Hagen, J., Flier, J. S., Lowell, B. B. (1995). Targeted Disruption of the beta(3)-Adrenergic Receptor Gene. J. Biol. Chem. 270: 29483-29492 [Abstract] [Full Text]  
• (1995). . . . and a Human Obesity Gene Is Identified. JWatch Psychiatry 1995: 17-17 [Full Text]  
• (1995). . . . and a Human Obesity Gene Is Identified. Journal Watch Dermatology 1995: 15-15 [Full Text]  
• (1995). ...AND A SECOND OBESITY GENE IS IDENTIFIED. JWatch General 1995: 2-2 [Full Text]  
• Walston, J., Silver, K., Bogardus, C., Knowler, W. C., Celi, F. S., Austin, S., Manning, B., Strosberg, A. D., Stern, M. P., Raben, N., Sorkin, J. D., Roth, J., Shuldiner, A. R. (1995). Time of Onset of Non-Insulin-Dependent Diabetes Mellitus and Genetic Variation in the {beta}3-Adrenergic-Receptor Gene. NEJM 333: 343-347 [Abstract] [Full Text]  
• Arner, P. (1995). The {beta}3-Adrenergic Receptor -- A Cause and Cure of Obesity?. NEJM 333: 382-383 [Full Text]