FTO基因SNP rs9939609,rs1421085多态性与儿童青少年肥胖及其代谢指标的相关性研究

Association of FTO gene rs9939609,rs1421085 single nucleotide polymorphisms with obesity and matabolic parameters in Chinese Han children and adolescents

目的研究FTO(fat-mass and obesity associated)基因SNP rs9939609和rs1421085多态性与儿童青少年单纯性肥胖及其代谢指标的相关性。方法以2004至2006年于复旦大学附属儿科医院内分泌门诊就诊的汉族单纯性肥胖和超重儿童青少年分别作为肥胖组和超重组;选择上海市某中学正常体重汉族学生作为正常对照组。分别测量身高和体重,计算BMI。测定血清空腹葡萄糖(FPG)、空腹胰岛素(FIns)、三酰甘油(TG)和总胆固醇(TC)水平。计算胰岛素抵抗指数(HOMA-IR)和胰岛素敏感指数(QUICKI)。抽提外周血基因组DNA,采用Taqman-MGB探针技术检测FTO基因SNPrs9939609和rs1421085多态性,分析不同基因型与代谢指标和BMI的相关性。结果肥胖组纳入236例,超重组纳入239例,正常对照组纳入241名。肥胖+超重组的BMI、FPG、FIns、TG和HOMA-IR显著高于正常对照组;②肥胖、超重和正常对照组rs9939609分型成功率分别为94.9%(224/236例)、97.9(234/239例)和95.9%(231/241名),rs1421085分型成功率分别为92.8%(219/236例)、97.1%(232/239例)和95.4%(230/241名)。rs9939609AA基因型频率:肥胖组为2.7%,超重组为0.4%,正常对照组为1.7%,肥胖+超重组A等位基因频率显著高于正常对照组(OR=1.437,P=0.048);rs1421085CC基因型频率:肥胖组为2.7%,超重组为0.9%,正常对照组为1.7%,肥胖+超重组C等位基因频率高于正常对照组,但差异无统计学意义(OR=1.388,P=0.0760);③rs1421085TC+CC基因型和rs9939609TA+AA基因型儿童青少年的BMI显著高于TT基因型(rs9939609:P=0.0003;rs1421085:P=0.0005);rs1421085TC+CC基因型和rs9939609TA+AA基因型与FPG、FIns、TG、TC、HOMA-IR、QUICKI无显著相关性。结论FTO基因SNP rs9939609和rs1421085多态性与中国汉族儿童青少年肥胖和(或)超重存在相关性。A等位基因频率远低于欧洲人群,对BMI的作用效果与欧洲人群相似,但对代谢指标影响存在显著差异。

Objective To investigate the role of the FTO gene rs9939609, rs1421085 polymorphism on obesity and relative trials in Chinese Han children and adolescents. Methods Obese/overweights children and adolescents and normal weight children as control aged 6 - 18 years old were enrolled. Body height and weight were measured and body mass index （BMI） was calculated. Serum fasting plasm glucose （FPG） , fasting insulin （Fins） , triglycerid （TG） and cholesterol （TC） were measured. HOMA-IR and QUICKI were calculated. Genomie DNA was extracted from peripheral blood, Taqman-MGB probe was used to detect the FTO rs9939609, rs1421085 polymorphism. Obesity was evaluated by using IOTF BMI standard. Results Obesity group, overweight group and normal control group included 236,239 and 241 children, respectively. ①The levels of FPG, Fins, TG and HOMA-IR were significantly higher in obesity/overweight group than that in normal control group.②The successful rates of m9939609 typing in obesity group, overweight group and normal control group were 94. 9% （224/236） ,97.9% （234/239） and 95.9% （231/241）, respectively. The successful rates of rs1421085 typing in obesity group, overweight group and normal control group were 92. 8% （219/236） ,97. 1% （232/239） and 95.4% （230/241） , respectively. The AA genotype frequency of rs9939609 was 2.7% in obesity group and 0.4% in overweight group and there existed significant difference compared with normal control group（ genotype frequency 1.7% ,P =0. 048, OR = 1. 437）. The CC genotype frequency of rs1421085 was 2.7% in obesity group and 0. 9 % in overweight group and there existed significant difference compared with normal control group（ genotype frequeney 1.7% ,P = 0. 076, OR = 1. 388）. ③There existed significant difference in BMI between the rs1421085 TC ＋ CC, rs9939609 TA ＋ AA genotypes when compared with their wild TT genotypes（ rs9939609： P = 0. 000 3; rs1421085： P =0. 000 5 ）. However, FPG, Fins, TG, TC, HOMA-IR and QUICKI showed no significant difference between the rs1421085 TC ＋ CC, rs9939609 TA ＋ AA genotypes and their wild TT genotypes was not found. Conclusions FTO gene rs9939609 and rs1421085 SNP was firstly reported to be associated with obesity and BMI in Chinese Han children and adolescents, but the significant statistical association among the SNPs and obesity related metabolic parameters.