Abstract: AbstractObjectiveTo search for mutations in the MC4R in obese and normal weight Chinese children. MethodsScreen the coding region of the MC4R gene by PCR and resequencing.The clinical and biochemical data of 200 obese children were analysed. ResultsIn the obese children we detected two heterozygotes for novel nonsynonymous mutations (c.496G>A resulting in Val166Ile;c.929G>A resulting in Arg310Lys) and a heterozygote for a novel nonsense mutation (c.831T>A resulting in a premature stop codon Cys277Stop) in the MC4R gene in three of the obese individuals.In both,the obese individuals and the normal weight controls heterozygotes for a novel nonsynonymous mutation (c.68T>G resulting in Leu23Arg,0.5% and 1%,respectively) and the Val103Ile (c.307G>A,3%and 2%,respectively).We analysed ALT、AST、TG、CHO and WBISI in mutation and nonmutation obese group and found there were no difference.Heterozygotes for the Val103Ile polymorphism were detected in similar frequencies in obese and normal weight controls.The prevalence for heterozygous MC4R mutations was 1.5% in the obese. ConclusionTwo novel heterozygous nonsynonymous mutations (Val166Ile;Arg310Lys) and a novel heterozygous nonsense mutation (Cys277Stop) are detected in Chinese obese individuals.Leu23Arg variant might be a polymorphism in the Chinese population.

Key words: Sequencing, Obesity, Children , Heterozygote

摘要： 目的探讨肥胖儿童黑皮质素4受体(MC4R)的突变频率及其与临床生化指标改变的关系。 方法浙江大学医学院附属儿童医院等单位于2004—2005年，对200例肥胖及100例正常体重儿童，利用PCR及基因测序技术进行MC4R基因筛查，同时对200例肥胖儿童进行生化检测和口服葡萄糖耐量试验。 结果(1)200例肥胖儿童中检出杂合子错义突变、无义突变3例；100例对照组中未检出突变;Val103Ile基因多态性在两组中分别有6例、2例。肥胖组中发现了3个新的杂合子突变位点Val166Ile、Cys277Stop、Arg310Lys；肥胖组和对照组中同时检测到新的杂合子变异Leu23Arg。(2)MC4R突变组和非突变组的肥胖儿童BMI、ALT、AST、TG、CHO、WBISI比较均无统计学意义(P>0.05)。 结论(1)首次在汉族儿童人群中发现了MC4R基因3个新的杂合子突变位点(Val166Ile、Cys277Stop、Arg310Lys)。(2)Leu23Arg可能是汉族人群MC4R的基因多态性。

关键词: 黑皮质素4受体, 杂合子, 测序, 肥胖, 儿童