The Relationship Of Leptin Receptor Gene Polymorphisms With Polyunsaturated Fatty Acids In Obese Children

OBJECTIVES:To investigate the relationships between leptin receptor gene Gln223Arg and Pro1019Pro polymorphisms with polyunsaturated fatty acids and the clinical characters of obesity in obese children.To know the function of leptin receptor gene polymorphisms in the pathogenesis of childhood obesity and whether the plasma levels of polyunsaturated fatty acids changed in obese children.To provide science evidence for further understanding of the pathogenesis of childhood obesity and methods for treating childhood obesity.METHODS:166 obese children were chosen from the primary schools of Kaifu district of Changsha city and the obese ones visited in our out-patient department,and 148 normal weight children whose age and sex were macthed with the obese ones were enrolled in the study.All children were evaluated for height,weight,waist circumference(WC),systolic blood pressure(SBP) and diastolic blood pressure(DBP).Triglyceride(TG), total cholesterol(TC),high density lipoprotein-cholesterol(HDL-C),low density lipoprotein-cholesterol(LDL-C) were determined by automatic biochemistry analyzer.The percentage of body fat(PBF) was tested by dual-energy X-ray absorptiometry(DEXA).The fasting plasma glucose(FPG) was detected by glucose oxidase.The fasting plasma insulin (FINS) was tested by radioimmunoassay(RIA).The plasma level of leptin was examined by enzyme-linked immunosorbent assay(ELISA).The plasma levels of PUFAs ware deteccted by gas chromatograhpy/mass spectrometry(GC/MS).Body mass index(BMI),waist to height ratio (WHtR) and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated.The Gln223Arg and Pro1019Pro polymorphisms of LEPR gene were tested by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) assay. Samples were randomly selected for direct sequencing to identify the results of PCR-RFLP.RESULTS:①The obese children had higher BMI,PBF,WC,WHtR, TG,TC and LDL-C as compared with the normal ones.②The levels of FINS,leptin and HOMA-IR in obese children were higher than that of normal ones.③The levels of n-3PUFAs in obese children were higher than that in normal ones,while the n-6PUFAs and total PUFAs levels were lower.The level of n-3PUFAs was positvely correlated with leptin level.④Multiple stepwise regression analysis showed AA,DPA and ALA were significant predictors of PBF,while AA,DPA,ALA and C20:3n-6 were influencing factors of leptin.④The genotype and allele frequencies of leptin receptor gene Gln223Arg in obese group were different from that of normal group.The Gln223Arg polymorphisms was associated with PBF,BMI,TG,TC and HOMA-IR in obese children.There was no diffference in the genotype and allele frequencies of LEPR gene Pro1019Pro between the obese group and normal group.The clinical features had no significant difference between different genotypes of LEPR gene Pro1019Pro.⑤The GA+AA genotype obese children had higer n-3PUFAs,total PUFAs and n-6PUFAs levels as compared with the GG genotype of LEPR gene Gln223Arg.There was no significant difference in PUFAs level between different genotypes of LEPR gene Pro1019Pro.⑥Linkage disequilibria analysis showed the two loci reached linkage equilibria.CONCLUSIONS:①There are hyperleptinemia and leptin resistance in obese children.②The PUFAs levels change in obese children,n-3 PUFAs levels increase,while the levels of n-6PUFAs and total PUFAs decrease.③LEPR gene Gln223Arg polymorphisms is associated with childhood obesity and the disorder of PUFAs metabolism in obese children,G allele is the protective factor of obesity in children.④There is no significant association of LEPR gene Pro1019Pro polymorphisms with childhood obesity and the disorder of PUFAs metabolism in obese children.