南京地区单纯性肥胖患儿黑皮素4受体基因筛查

Gene Mutation Screening of Melanocortin 4 Receptor of Simple Obese Children in Nanjing City

目的对南京单纯性肥胖患儿进行黑皮素4受体(Mc4R)基因筛查,了解南京单纯性肥胖患儿Mc4R基因的突变情况。方法105例单纯性肥胖患儿(肥胖组)体质量指数(BMI)参照中国学龄儿童青少年超重、肥胖筛查体重指数值分类标准(中国肥胖问题工作组2004年标准),且各项检查排除内分泌和遗传代谢疾病。男58例,女47例;年龄为(10.32±2.99)岁;BMI为(27.61±2.51)kg.m-2。健康对照组为体检健康儿童127例。男67例,女60例;年龄(8.78±2.95)岁;BMI(16.87±2.32)kg.cm-2。家长均知情同意。采用梯度PCR扩增,对Mc4R基因进行测序。比较肥胖组和健康对照组患儿生化指标(ALT、AST、总蛋白、清蛋白、球蛋白、清蛋白/球蛋白、三酰甘油、总胆固醇、高密度脂蛋白和皮质醇、胰岛素、C肽)。结果肥胖组与健康对照组血三酰甘油,空腹与餐后2h胰岛素、C肽及BMI比较差异均有统计学意义(Pa<0.05)。IVa110311e杂合子在肥胖组和健康对照组的发生率分别为2.86%(3/105例)和0(0/127例)。肥胖组患儿中3例IVa110311e杂合子携带者生化指标与其他肥胖患儿比较差异无统计学意义。结论IVa110311e是南京单纯性肥胖儿童Mc4R基因变异的主要因素之一。

Objective To screen melanocortin 4 receptor （Mc4R） gene mutation by direct DNA sequencing in order to explore the mutation situation of Mc4R gene in simple obese children in Nanjing.Methods One hundred and five simple obese children（obesity group） and 127 healthy children（healthy control group） were examined for mutations of Mc4R gene.Body mass index（BMI）cutoff points for overweight and obesity adopted Chinese children and adolescents,recommended by China Working Group of Obesity,and all children had no other hereditary and metabolic abnormality.Touch-down PCR was performed to amplify the full length Mc4R gene,then direct DNA sequencing was used to analyze the Mc4R gene.The differences of biochemical index levels between obesity group and healthy control group were analyzed ,including alanine transaminase,aspartate transaminas,total protein,albumin,globulin,albumin/globulin,triglyceride,cholesterol,high density lipoprotein,cortisol,insulin and C peptide.Results There were significant differences of biochemical index levels between obesity group and healthy control group,including triglyceride,insulin level after dining 2 h,C peptide and BMI（Pa0.05）.Three reported single nucleotide polymorphism IVa110311e were found in obesity children（2.86%）,but not in healthy control group.There was no difference of biochemical index between 3 children with IVa110311e mutation and other obese children without mutation in obesity group.Conclusion IVa110311e is a major cause of Mc4R gene variation in Nanjing simple obese children.