F261S——肥胖患者中黑皮素4受体基因的新突变  

F261S——A novel mutation of melanocortin 4 receptor gene in the obese patients

作　　者：蔡姝冰[1] 贾伟平 方启晨[1] 邵新[1] 张蓉[1] 项坤三[1] 

机构地区：[1]上海市糖尿病研究所

出　　处：《中华内分泌代谢杂志》2004年第4期372-375,共4页Chinese Journal of Endocrinology and Metabolism

基　　金：上海市科技发展基金项目(99XD14017);上海市卫生系统百名跨世纪优秀学科带头人培养计划项目(97BR039)

摘　　要：目的对中国肥胖人群进行黑皮素4受体(MC4R)基因全长(包括编码区及侧翼区)进行筛查,以了解中国人该基因突变的情况。方法选取BMI≥30kg/m2的无亲缘关系的上海地区中国人256例,用聚合酶链反应单链构象多态性(PCRSSCP)技术对MC4R基因全长进行筛查,对异常片段进行测序。用聚合酶链反应限制性片段长度多态性(PCRRFLP)对320名健康对照者进行相应位点的突变检测。结果肥胖患者中发现MC4R一种错义突变,第261位氨基酸发生Phe261Ser改变,即F261S。突变携带者皆超重/肥胖,突变纯合子肥胖程度大于杂合子。突变携带者不伴有其它内分泌异常。此外,还见到3种变异,其中2种为尚未报道的变异:nt124C→G及Leu59Leu;另一种为既往报道过的Ile103Val。结论F261S突变为中国人中首次报道的MC4R基因突变。MC4R基因突变可能是中国人肥胖病发生的一个原因。Objective To screen a Chinese obese population for melanocortin 4 receptor (MC4R) gene mutations by single-strand conformational polymorphism (SSCP). Methods In the research, 256 unrelated obese Chinese (BMI≥30 kg/m^(2)) were examined for mutations at MC4R locus. Polymerase chain reaction (PCR) was performed to amplify the MC4R gene, including coding region, 3′-and 5′-flanking region. PCR products were screened using the single-strand conformation polymorphism (SSCP) analysis, and then the direct DNA sequencing. PCR-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the MC4R mutation in 300 healthy lean controls. Genetic analysis and clinical tests were undertaken in the proband MC4R mutation and his family members. Results A novel homozygous missense mutation, F261S, was identified. The homozygous is more obese than the heterozygous. Anterior pituitary-derived hormones of the pedigree members were within normal limits. In addition, one polymorphism (nt -124C→G), one silent mutation Leu59, and one reported mutationI103V were found in the Chinese. Conclusion One novel missense MC4R mutation, F261S, is found in the Chinese population for the first time. MC4R gene mutation seems to be an important cause of obesity in Chinese papulation.

关 键 词：突变 肥胖患者 MC 携带者 筛查 中国人 聚合酶链反应 R基因 编码区 测序 

分 类 号：R589.2[医药卫生—内分泌] R512[医药卫生—内科学]