GENETIC-VARIATION IN THE BETA(3)-ADRENERGIC RECEPTOR AND AN INCREASED CAPACITY TO GAIN WEIGHT IN PATIENTS WITH MORBID-OBESITY
GENETIC-VARIATION IN THE BETA(3)-ADRENERGIC RECEPTOR AND AN INCREASED CAPACITY TO GAIN WEIGHT IN PATIENTS WITH MORBID-OBESITY
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DOI：
10.1056/nejm199508103330605
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发表时间：
1995-08-10
影响因子：
158.5
通讯作者：
STROSBERG, AD
中科院分区：
文献类型：
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作者：
CLEMENT, K;VAISSE, C;STROSBERG, AD
背景β（3）肾上腺素能受体主要位于脂肪组织中，参与脂解和产热的调节。该受体与人类肥胖的潜在相关性使我们筛选法国肥胖患者中最近发现的受体基因突变。我们使用聚合酶链反应扩增了β 3肾上腺素能受体基因的一个区域，该区域编码从185名病态肥胖患者（体重指数[体重（千克）除以身高（米）的平方]，>40）和94名正常受试者的白细胞中提取的基因组DNA中的氨基酸残基27至110。通过限制性片段长度多态性分析检测到一个导致色氨酸在第64位被精氨酸取代的突变（Trp 64 Arg），该分析使用核酸内切酶BstNI，其区分正常和突变序列。病态肥胖患者和正常人中Trp 64 Arg等位基因的频率相似（分别为0.08和0.10），然而，Trp 64 Arg突变杂合子的病态肥胖患者增重能力增加; 14例杂合子患者的平均体重为140 kg，而171例无突变患者的平均体重为126 kg Trp 64 Arg杂合子的25年累积体重变化（从20岁算起）为67 kg，而非Trp 64 Arg杂合子的25年累积体重变化为51 kg。Trp 64 Arg杂合子患者的最大体重差（最大终生体重减去20岁时的体重）为74 kg，而非突变患者为59 kg（P=0.02）。β（3）-肾上腺素能受体基因Trp 64 Arg突变的人可能会增加体重。
Background. 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.Methods. 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 BstNI, 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 beta(3)-adrenergic receptor may have an increased capacity to gain weight.