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

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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.

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