Lubrano-Berthelier Cecile, Dubern Beatrice, Lacorte Jean-Marc, Picard Franck, Shapiro Astrid, Zhang Sumei, Bertrais Sandrine, Hercberg Serge, Basdevant Arnaud, Clement Karine, Vaisse Christian
Diabetes Center and Department of Medicine, University of California San Francisco, San Francisco, California 94143-0573, USA.
J Clin Endocrinol Metab. 2006 May;91(5):1811-8. doi: 10.1210/jc.2005-1411. Epub 2006 Feb 28.
Heterozygous mutations in the melanocortin-4 receptor (MC4R) gene are the most common monogenic form of severe obesity in children. There are conflicting reports regarding the prevalence, nature, and pathogenic effects of MC4R mutations in adults with severe late-onset obesity.
Our objective was to determine the prevalence of MC4R mutations in a cohort of severely obese adults and to determine the clinical phenotype and the phenotype-genotype relationship within adult MC4R mutation carriers.
We conducted an observational study at a referral center.
Participants included 769 adult patients with body mass index of at least 35 kg/m(2) and 444 nonobese control individuals.
There were no interventions.
We assessed the prevalence of pathogenic MC4R mutations, functional characteristics of the detected mutations, phenotype, and phenotype-genotype relationship within mutation carriers.
The global prevalence of obesity-specific MC4R mutations was 2.6%, and the 95% confidence interval (CI(95)) was 1.5-3.7. The prevalence of MC4R mutations was similar in patients developing obesity in childhood (2.83%; CI(95), 0.9-4.8) and in patients with a later onset of the disease (2.35%; CI(95), 0.9-3.8). Adult obese MC4R mutation carriers did not present with binge eating or with any specific clinical phenotype. The severity of the functional alterations of the mutated MC4Rs and in particular the intracellular retention of the receptor correlates both with the severity and the onset of the obesity in the mutation carriers.
Obese adult carriers of functionally relevant MC4R mutations do not specifically present with binge-eating disorder or a history of early-onset obesity. The onset and severity of the obesity in the carriers is related to the functional severity of the MC4R mutations.
黑皮质素4受体（MC4R）基因的杂合突变是儿童严重肥胖最常见的单基因形式。关于严重迟发性肥胖成人中MC4R突变的患病率、性质和致病作用，存在相互矛盾的报道。
我们的目的是确定一组严重肥胖成人中MC4R突变的患病率，并确定成人MC4R突变携带者的临床表型以及表型与基因型的关系。
我们在一家转诊中心进行了一项观察性研究。
参与者包括769名体重指数至少为35kg/m²的成年患者和444名非肥胖对照个体。
未采取干预措施。
我们评估了致病性MC4R突变的患病率、检测到的突变的功能特征、表型以及突变携带者内部的表型与基因型关系。
肥胖特异性MC4R突变的总体患病率为2.6%，95%置信区间（CI(95)）为1.5 - 3.7。儿童期发生肥胖的患者中MC4R突变的患病率（2.83%；CI(95)，0.9 - 4.8）与疾病发病较晚的患者中相似（2.35%；CI(95)，0.9 - 3.8）。成年肥胖MC4R突变携带者未出现暴饮暴食或任何特定的临床表型。突变型MC4R功能改变的严重程度，特别是受体的细胞内滞留，与突变携带者肥胖的严重程度和发病情况均相关。
功能相关的MC4R突变的肥胖成年携带者未特别表现出暴饮暴食症或早发性肥胖史。携带者肥胖的发病和严重程度与MC4R突变的功能严重程度有关。
