长沙市开福区儿童肥胖的影响因素分析及与PTP1B基因多态性的关系
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摘要
第一章长沙市开福区儿童肥胖的现状及影响因素分析
     目的:了解长沙市开福区儿童超重、肥胖流行情况及肥胖的影响因素,为儿童肥胖的防治工作提供科学依据。
     方法:随机抽取长沙市开福区7~12岁儿童4140名,按照体重指数(BMI)法判定出肥胖,将肥胖和健康儿童设为病例组和对照组。应用问卷调查302名肥胖儿童和301名健康儿童的饮食行为和运动行为。进一步对147名肥胖儿童和118名健康儿童进行腰围(WC)、腰臀比(WHR)、体脂百分比(%BF)、收缩压(SBP)、舒张压(DBP)、空腹血糖(FPG)、血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)检测。
     结果:①长沙市开福区儿童超重、肥胖检出率分别为9.76%和7.39%,男、女生肥胖率分别为9.37%和5.13%。②男生肥胖的危险因素可归结为进餐速度快、常吃西式快餐、看电视时间长、常吃甜食、常吃油腻食物,而运动时间长具有保护作用;女生肥胖的危险因素可归结为常暴饮暴食、看电视时间长、常吃甜食,而运动时间长具有保护作用。③与健康儿童相比,肥胖儿童的BMI、WC、WHR、%BF、SBP、TG和LDL-C明显升高,HDL-C明显降低。④多元逐步回归分析显示,影响男生%BF因素的顺序依次为BMI、WC和WHR,影响女生%BF因素的顺序依次为BMI、WC。
     结论:①长沙市开福区儿童肥胖的发生率在国内处于高水平,男生的超重及肥胖率明显高于女生。②不良的饮食行为和缺乏运动是引起儿童肥胖的主要原因。③肥胖儿童的SBP、TG、LDL-C明显高于健康儿童,HDL-C明显低于健康儿童。
     第二章PTP1B基因多态性与儿童肥胖的关系
     目的:蛋白酪氨酸磷酸酶1B(PTP1B)影响瘦素和胰岛素信号传导以及脂代谢等,分析儿童PTP1B基因ⅣS6+G82A与Pro303Pro多态性分布特征,探讨ⅣS6+G82A与Pro303Pro遗传多态性在儿童单纯性肥胖发病机制中的作用。
     方法:选择147例肥胖儿童及118例健康儿童,应用放射免疫法(RIA)法测定空腹胰岛素水平(FINS),计算稳态模型胰岛素抵抗指数(HOMA-IR),酶联免疫法(ELISA)测定瘦素水平。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测PTP1B基因ⅣS6+G82A与Pro303Pro多态性。随机选择部分样品应用直接测序法验证PCR-RFLP结果。
     结果:①肥胖儿童FINS、HOMA-IR、瘦素较健康儿童均明显升高。多元逐步回归分析显示,影响男生瘦素水平的顺序依次为BMI、FINS和%BF,影响女生瘦素水平的顺序依次为BMI、FINS。②健康儿童PTP1B基因ⅣS6+G82A与Pro303Pro多态性发生频率分别为53.4%与11.0%。肥胖儿童PTP1B基因ⅣS6+G82A多态性发生频率为59.5%,与健康儿童无显著性差异,且该位点突变与肥胖儿童临床指标无明显相关性。肥胖儿童PTP1B基因Pro303Pro多态性发生频率为19.4%,与健康儿童相比,基因型分布与等位基因频率均存在显著性差异,并且发现肥胖儿童Pro303Pro多态性与BMI、WC、TG和LDL-C水平有关。③对ⅣS6+G82A与Pro303Pro进行了连锁不平衡分析(D′:0.441,r~2:0.027),则两位点间连锁不平衡很弱。
     结论:①肥胖儿童存在胰岛素抵抗和瘦素抵抗。②本研究明确了PTP1B基因ⅣS6+G82A与Pro303Pro遗传多态性在健康儿童和肥胖儿童中的分布特征。③PTP1B基因ⅣS6+G82A变异与儿童单纯性肥胖无明显相关性,而Pro303Pro变异可能与儿童单纯性肥胖相关,且影响肥胖儿童的脂质代谢。
Chapter 1 The study on obesity and its risk factors in children in Kai fu District in Changsha
     OBJECTIVES:To study the prevalence of overweight and obesity and the risk factors to obesity in children in Kai fu District in Changsha and to provide the scientific evidence for prevention and control of obesity in children.
     METHODS:A total of 4140 children aged 7 to 12 years old in Kai fu District in Changsha were randomly selected and obesity was assessed by the method of body mass index(BMI).Children were divided into obesity and control groups.A totle of 302 obese and 301 health children were investigated by questionnaires including dietary habits and physical exercise habits.Further,147 obese and 118 health children were selected and their waist circumference(WC),waist to hip ratio(WHR),percentage of body fat(%BF),systolic blood pressure(SBP),diastolic blood pressure (DBP),fasting plasma glucose(FPG),serum triglycerides(TG),total cholesterol(TC),high density lipoprotein-cholesterol(HDL-C)and low density lipoprotein-cholesterol(LDL-C)were tested.
     RESULTS:①The prevalence rates of overweight and obesity in children in Kai fu District in Changsha were 9.76%and 7.39%respectively, and the obesity rates of boys and girls were 9.37%and 5.13%respectively.②The risk factors of obesity in boys included fast speed of eating, partiality for western fast food,long time to watch television,partiality for sweet foods,partiality for fried foods and the protective factors included long time to exercise.The risk factors of obesity in girls included excessive drinking and eating,long time to watch television,partiality for sweet foods and the protective factors included long time to exercise.③Obesity group had higher BMI,WC,WHR,%BF,SBP,TG,LDL-C and lower HDL-C as compared with those of control group.④The multiple stepwise regression analysis showed that BMI,WC and WHR were the main factors for%BF in boys and BMI,WC were the main factors for%BF in girls.
     CONCLUSION:①The prevalence of obesity is at a high level in China and the rates of overweight and obesity are greater in boys than in girls.②Unhealthy eating behavior and lack of physical activity are main causes of childhood obesity.③Obesity group has higher SBP,TG,LDL-C and lower HDL-C in comparison to controls. in children and to determine the effects of PTP1B gene IVS6+G82A and Pro303Pro polymorphisms on the pathogenesis of childhood obesity.
     METHODS:A totle of 147 obese and 118 health children were selected.The plasma fasting insulin(FINS)levels of children were measured by radioimmunoassay(RIA).Homeostasis model assessment for insulin resistance(HOMA-IR)were calculated.The plasma leptin levels of children were measured by enzyme-linked immunosorbent assay(ELISA). The IVS6+G82A and Pro303Pro polymorphisms of PTP1B gene were tested by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay.Samples were randomly selected to direct sequencing to identify the results of PCR-RFLP.
     RESULTS:①Obesity group had higher FINS、HOMA-IR、leptin levels as compared with those of control group.The multiple stepwise regression analysis showed that BMI,FINS and%BF had main effects on leptin in boys and BMI,FINS had main effects on leptin in girls.②The allele frequencies of PTP 1B gene IVS6+G82A and Pro303 Pro were 53.4% and 11.0%in control group,respectively.In obese group,the allele frequencies for IVS6+G82A and Pro303Pro were 59.5%and 19.4%, respectively.We did not find any differences in the genotype distributions or allele frequencies of IVS6+G82A polymorphisms between obese and control group.Further analysis showed no association between genotypes of IVS6+G82A and clinical characteristics in obese subjects.There were significant differences in genotype and allele frequencies of the Pro303Pro polymorphism between the two studied groups.In addition,the Pro303Pro polymorphism was associated with BMI,WC,TG and LDL-C in obese subjects.③The linkage disequilibrium analysis was carried out for IVS6+G82A and Pro303Pro(D':0.441,r~2:0.027),so their linkage disequilibrium was weak.
     CONCLUSIONS:①Insulin resistance and leptin resistance are present in obese children.②The distribution characteristics of PTP1B gene IVS6+G82A and Pro303Pro polymorphisms in obese and healthy children are identified.③There is no significant association of PTP1B gene IVS6+G82A variant with obesity in children.But Pro303Pro variant may be associated with obesity in children and affects the lipid metabolism in obese children.
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