Clément K, Vaisse C, Manning B S, Basdevant A, Guy-Grand B, Ruiz J, Silver K D, Shuldiner A R, Froguel P, Strosberg A D
Centre National de la Recherche Scientifique, Unité CNRS-EP10, Institut Pasteur, Lille, France.
N Engl J Med. 1995 Aug 10;333(6):352-4. doi: 10.1056/NEJM199508103330605.
The beta 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.
We used the polymerase chain reaction to amplify a region of the gene for the beta 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 BstNl, which discriminates between the normal and mutant sequences.
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).
People with the Trp64Arg mutation of the gene for the beta 3-adrenergic receptor may have an increased capacity to gain weight.
β3 - 肾上腺素能受体主要位于脂肪组织，参与脂肪分解和产热的调节。该受体与人类肥胖潜在的相关性促使我们对肥胖的法国患者进行筛查，以寻找该受体基因中最近发现的突变。
我们使用聚合酶链反应扩增β3 - 肾上腺素能受体基因的一个区域，该区域编码从185例病态肥胖患者（体重指数[千克体重除以米身高的平方]，> 40）和94名正常受试者的白细胞中提取的基因组DNA中的第27至110个氨基酸残基。通过使用内切酶BstNl进行限制性片段长度多态性分析来检测导致第64位色氨酸被精氨酸取代（Trp64Arg）的突变，该酶可区分正常和突变序列。
Trp64Arg等位基因在病态肥胖患者和正常受试者中的频率相似（分别为0.08和0.10）。然而，携带Trp64Arg突变杂合子的病态肥胖患者体重增加能力增强；14名杂合子患者的平均体重为140千克，而171名未发生突变的患者平均体重为126千克（P = 0.03）。该样本中无纯合子。Trp64Arg杂合子25年（从20岁起）的体重累积变化为67千克，而未发生突变者为51千克。Trp64Arg杂合子的最大体重差异（最大终身体重减去20岁时的体重）为74千克，未发生突变的患者为59千克（P = 0.02）。
β3 - 肾上腺素能受体基因发生Trp64Arg突变的人可能体重增加能力增强。
