瘦素抵抗与载脂蛋白E基因多态性对儿童血脂的影响

Effects of the Leptin Resistance and the Polymorphism for Apolipoprotein E Gene on the Children's Lipid Metabolism

目的探讨瘦素（leptin）及瘦素抵抗与载脂蛋白（apoprotein,Apo）E基因多态性对肥胖儿童脂质代谢的影响,为肥胖所致相关疾病提供早期预防措施。方法选择2009年7月至2010年10月在本院门诊就诊、住院确诊及体检时发现的儿童肥胖症患儿99例（研究组）和健康儿童76例（对照组）,年龄均为6~14岁。对研究组儿童,再根据瘦素水平分为瘦素抵抗型组（〉9.21ng/mL,n=71）和瘦素敏感型（〈9.21ng/mL,n=28）。对研究组和对照组儿童禁食12h后抽取外周静脉血,测定血清血脂水平[总胆固醇（total cholesterol,TC）,甘油三酯（triglyceride,TG）,高密度脂蛋白（high densitylipoprotein,HDL）-C,低密度脂蛋白（low density lipoprotein,LDL）-C）]。采用放射性免疫分析法测定血清瘦素水平。采用聚合酶链式反应-限制性片段多态性（polymerase chain reaction restrictionfragment length polymorphism,PCR-RFLP）及聚丙烯酰胺凝胶电泳法测定儿童载脂蛋白E基因型。测定两组儿童身高及体重,计算体重指数（body mass index,BMI）。结果与对照组儿童比较,研究组儿童存在血脂代谢紊乱及血清瘦素水平增高,72%肥胖症儿童存在瘦素抵抗。肥胖儿童中瘦素抵抗组血清总胆固醇、甘油三酯和低密度脂蛋白-C显著高于瘦素敏感组,高密度脂蛋白-C显著低于瘦素敏感组。本实验共检出4种载脂蛋白E基因型,分别为E3/3型,E4/3型,E2/3和E4/2型。与健康儿童比较,肥胖儿童ε4等位基因频率增高。携带ε4等位基因个体中,瘦素抵抗型个体与瘦素敏感型个体比较,具有较高的血清总胆固醇、甘油三酯和低密度脂蛋白-C浓度。非携带ε4个体中,瘦素抵抗型个体与瘦素敏感型个体比较,具有较高的血血清总胆固醇、低密度脂蛋白-C浓度,和较低的高密度脂蛋白-C浓度。携带ε4且瘦素抵抗型个体与非携带ε4且瘦素抵抗型个体比较,血清总胆固醇、甘油三酯和低密度脂蛋白-C浓度升高。结论肥胖症儿童存在瘦素抵抗,其载脂蛋白E基因多态性存在变化,二者可明显影响血脂水平,临床上表现为携带ε4且瘦素抵抗型个体更易发生血脂代谢紊乱。

Objective To investigate the effects of leptin and its resistance,the polymorphism for apolipoprotein（Apo）E gene on the lipid metabolism in the children with obesity,provide precautionary measure for disease caused by obese.Methods From 99 obese children and 76 healthy children from 6-14 years old were chosen as obese group and healthy group.The vein blood of the children in the two groups were got after fasting over 12 hour.Then the serum lipid（TC,TG,HDL-C,LDL-C）were assayed,serum levels of leptin was measured 1 by RIA.Polymerase chain reaction-restricted fragments length polymorphism（PCR-RFLP）and polyacrylamide gelelectrophoresis were used for the detection of apolipoprotein E genotype.Results Compared with the healthy group,lipid metabolism disorders inherented in obese group and the serum levels of leptin in obese group was higher.72% of obese children were leptin resistant.Serum levels of TC,TG,LDL-C were higer,HDL-C was lower in obesity leptin resistance group,compared with those in obesity leptin sensitive group.Four genetype of ApoE（E3/3 E4/3 E2/3 E4/2）were detected.Compared with the healthy group,the frequency of ε4 allele in obesity group was higer.Compared with those of ε4 carrier and leptin sensitive obese children,the serum levels of TC,TG,LDL-C were higher in those of ε4 carrier and leptin resistance obese children.Compared with those of non ε4 carrier and leptin sensitive obese children,the serum levels of TC,LDL-C were higher,the HDL-C was lower.in those of non ε4 carrier and leptin resistance obese children.Compared with those of non ε4 carrier and leptin resistance obese children,the serum levels of TC,TG,LDL-C were higher in those of ε4 carrier and leptin resistance obese children.Conclusion leptin resistance and polymorphism of ApoE gene exist in obese children,which can influence the lipid metabolism clinically.Manifested as the possibility of lipid metabolism disorder in those of ε4 carrier and leptin resistance obese children were higher.