瘦素抵抗及其受体基因变异对单纯性肥胖患儿脂代谢的影响

Effect of Leptin Resistance and Leptin Receptor Gene Mutation on Lipid Metabolism in Simple Obese Children

目的探讨瘦素受体(LEPR)基因外显子突变与瘦素抵抗对单纯性肥胖患儿脂代谢的影响。方法选取6～14岁单纯性肥胖患儿102例(肥胖组)及非肥胖儿童83例(对照组)为研究对象,空腹12 h后抽取2组儿童外周静脉血,常规抽提基因DNA,用PCR限制性片断长度多态性及聚丙烯酰胺凝胶电泳法对2组儿童LEPR基因的第20外显子基因变异频率进行分析,采用放射性免疫分析法测定其血清瘦素水平及血清三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平及2组儿童身高和体质量。结果共检出3种LEPR基因第20外显子的基因型:AA型、AG型、GG型;与对照组儿童比较,单纯性肥胖患儿LEPR基因第3 057位核苷酸G→A突变率增高。AA基因型的肥胖患儿血清TC、TG、LDL-C水平均明显高于GG型者,而HDL-C水平低于后者。与对照组比较,肥胖组患儿存在血脂代谢紊乱,血清瘦素水平增高,79%存在瘦素抵抗。瘦素抵抗组患儿血清TC、TG、LDL-C显著高于瘦素敏感组,HDL-C低于瘦素敏感组。基因型为AA的瘦素抵抗者与基因型为GG的瘦素抵抗者比较,血清TG、LDL-C水平升高,HDL-C水平降低(Pa<0.05)。结论单纯性肥胖患儿存在瘦素抵抗及LEPR基因第20外显子基因突变,二者可影响儿童脂质代谢,且有一定的协同作用。临床表现为LEPR基因第20外显子AA基因型的瘦素抵抗个体更易发生血脂代谢紊乱。

Objective To investigate the effect of the variation of leptin receptor（LEPR） gene and leptin resistance on the lipid meta- bolism of the children with simple obesity. Methods One hundred and two simple obese children and 83 children without simple obesity aged 6 - 14 years old were chosen as the obese group and control group. The vein blood of the children in the 2 groups were got after fasting 12 hours. Polymerase chain reaction restriction fragment length polymorphism（RFLP） and polyacrylamide gel electrophoresis were used to ana- lyze the mutant frequency of the twentieth exon of the LEPR gene in the children in obesity group and control group. Then serum levels of lep- tin was measured by radioimmunoassay. At the same time, serum tfiglycefide （TG）, total cholesterol （TC）, high density lipoprotein cholesterol （ HDL - C ） ,low density lipoprotein cholesterol （ LDL - C ）, height and weight in all the children were measured. Results Three genotypes of the twentieth exon of LEPR gene had been detected in the research, they were AA, GA and GG;compared with control group, the frequency of the gene variation at 3 057 nucleotide G→A transversion was higher. The concentration of the serum TC ,TG and LDL - C of the simple obese children with AA genotype were higher and the level of the serum HDL - C was lower than those of children with the GG genotype （ P 〈 0. 01 ）. Compared with the control group, lipid metabolism disorders was inherent in obese group, and the serum levels of leptin in obese group was higher,79 % cases of simple obese children were leptin resistant. Serum levels of TC, TG, LDL - C in obesity leptin resistance group were higher, HDL - C was lower than those in obesity leptin sensitive group. Compared with simple obese children with GG genotype and leptin re- sistance ,the serum levels of TG and LDL - C were higher and the serum levels of HDL - C were lower in the children with AA genotype and leptin resistance. Conclusions Leptin resistance and mutation of twentieth exon of LEPR gene exist in simple obese children,which can in- fluence the lipid metabolism. Clinically manifested as the possibility of lipid metabolism disorder in simple obese children with AA genotype and leptin resistance are higher.