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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 effects of exon mutations of leptin receptor (LEPR) and leptin resistance on lipid metabolism in simple obese children. Methods Totally 102 children (obese group) and 83 non-obese children (obese group) aged 6-14 years old were enrolled in this study. Twelve hours after fasting, peripheral venous blood was collected from 2 children and routinely extracted DNA PCR restriction fragment length polymorphism and polyacrylamide gel electrophoresis analysis of two groups of children LEPR gene exon 20 gene mutation frequency analysis by radioimmunoassay serum leptin levels and serum triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and the height and weight of two groups of children. Results The genotypes of exon 20 of three LEPR genes were detected: AA, AG and GG. Compared with the control group, the mutation of nucleotide G → A at position 3 057 of LEPR gene in children with simple obesity Rate increased. The levels of TC, TG and LDL-C in obese children with AA genotype were significantly higher than those with GG type, while the HDL-C levels were lower than those in the latter. Compared with the control group, children with obesity had dyslipidemia, elevated serum leptin level, and leptin resistance 79%. Serum levels of TC, TG and LDL-C in leptin-resistant group were significantly higher than those in leptin-sensitive group, and HDL-C was lower than that in leptin-sensitive group. Serum TG, LDL-C levels were elevated and HDL-C levels were decreased (P <0.05) in leptin-resistant patients with genotype AA compared with leptin-resistant patients with genotype GG. Conclusion There is leptin resistance and mutation of exon 20 of LEPR gene in children with simple obesity. Both of them may affect lipid metabolism in children and have some synergistic effects. Leptin resistant individuals with clinical manifestations of the AA genotype of exon 20 of LEPR gene are more prone to dyslipidemia.