Ochoa M C, Azcona C, Biebermann H, Brumm H, Razquin C, Wermter A-K, Martínez J A, Hebebrand J, Hinney A, Moreno-Aliaga M J, Marti A, Patiño A, Chueca M, Oyarzabal M, Pelach R
Department of Physiology and Nutrition, University Clinic, University of Navarra, Pamplona (Navarra), Spain.
Clin Endocrinol (Oxf). 2007 May;66(5):652-8. doi: 10.1111/j.1365-2265.2007.02788.x.
The melanocortin 4 receptor gene (MC4R) is involved in body weight regulation. While many studies associated MC4R mutations with childhood obesity, information on MC4R mutations in Spanish children and adolescents is lacking. Our objective was to screen a population of children and adolescents from the north of Spain (Navarra) for MC4R mutations and to study the phenotypes of carriers and their families. In addition, functional assays were performed for a novel MC4R mutation.
The study was composed of 451 Spanish children and adolescents (49% boys), aged 5-18 year. According to the International Obesity Task Force (IOTF) criteria, the groups included 160 obese, 132 overweight and 159 normal-weight control subjects.
One novel (Thr162Arg) and three known nonsynonymous mutations in the MC4R gene (Ser30Phe, Thr150Ile, Ala244Glu) were detected heterozygously. The MC4R mutations were found in three male (one obese and two overweight) and two female subjects (one obese and one overweight). The novel mutation did not appear to lead to an impaired receptor function. An unequivocal relationship of MC4R mutations with obesity in pedigrees together with an impaired function of the encoded receptor could not be established for any of the mutations.
The presence of heterozygous MC4R mutations in obese and overweight subjects indicates that these mutations may be a susceptibility factor for obesity development, but lifestyle factors, such as exercise or sedentary activities, may modify their effect.
黑皮质素4受体基因（MC4R）参与体重调节。虽然许多研究将MC4R突变与儿童肥胖症相关联，但西班牙儿童和青少年中MC4R突变的信息尚缺。我们的目的是对西班牙北部（纳瓦拉）的儿童和青少年群体进行MC4R突变筛查，并研究携带者及其家族的表型。此外，对一种新的MC4R突变进行了功能测定。
该研究由451名西班牙儿童和青少年（49%为男孩）组成，年龄在5至18岁。根据国际肥胖特别工作组（IOTF）标准，这些组包括160名肥胖者、132名超重者和159名正常体重对照者。
杂合检测到MC4R基因中的一种新突变（Thr162Arg）和三种已知的非同义突变（Ser30Phe、Thr150Ile、Ala244Glu）。在三名男性（一名肥胖和两名超重）和两名女性受试者（一名肥胖和一名超重）中发现了MC4R突变。新突变似乎并未导致受体功能受损。对于任何一种突变，均无法在系谱中确定MC4R突变与肥胖之间明确的关系以及编码受体功能受损。
肥胖和超重受试者中存在杂合MC4R突变表明，这些突变可能是肥胖发生的易感因素，但生活方式因素，如运动或久坐活动，可能会改变其影响。
