脂联素血清水平和基因多态性与儿童肥胖及代谢紊乱的关联研究

发布时间：2018-03-17 08:10

本文选题：高分子脂联素　切入点：瘦素/高分子脂联素　出处：《北京协和医学院》2015年硕士论文　论文类型：学位论文

【摘要】：[目的](1)探讨血清高分子脂联素(High molecular weight adiponectin HMWAPN)、瘦素(Leptin)／高分子脂联素(L/HA)、瘦素／脂联素(L/A)比值与儿童代谢综合征(Metabolic syndrome MS)的相关性。(2)探讨血清总脂联素、高分子脂联素及瘦素与其比值与儿童青少年MHO的相关性。(3)探索及在中国人群汇总验证一些候选基因位点的多态性与脂联素水平的关联[方法]以2004年北京市儿童青少年代谢综合征(BcAMs)调查总样本中3520例6—18岁儿童为研究对象。代谢综合征的诊断采用修订的2007年IDF制定的标准。酶联免疫吸附法(ELISA)测定血清高分子脂联素、总脂联素和瘦素水平,多组间比较采用方差分析和卡方检验,Pearson相关分析HA、L/HA、L/A与代谢综合征各组分之间的相关性,受试者工作特征曲线下面积来探讨L/HA及L/A对儿童代谢综合征的诊断价值,逻辑回归探讨MHO的危险因素,协方差及多元线形回归分析SNP位点和血清脂联素的关系。[结果](1)随着L/HA、L/A值逐渐增大,BMI、WC、BP、FBG、LDL-C、TG呈进行性升高,中心性肥胖(CO%)、胰岛素抵抗情况(m%)越严重,代谢综合征检出率(MS%)越高：高分子脂联素的变化恰恰相反：(2)各组中含有MS危险因素数目越多,血清中L/HA、L/A值越高；(3)L/A值ROC曲线下面积大于L/HA及高分子脂联素曲线下面积。(4)肥胖人群中MHO比例为54.71%,MHO组具有较高的总脂联素及高分子脂联素水平；较低的LEP及L/HA水平,P0.05。(5) Logistic回归分析,发现降低的APN及升高的LEP为代谢异常肥胖的独立危险因素(P0.05)(6)首次在中国人群发现7个SNP位点有5个与两种脂联素水平关联,6个与总脂联水平相关。(7)首次发现其中CDH13 rs4783244与中国人群的总脂联素及高分子脂联素水平均高度关联,p值显著性水平分别达10-37—10-34[结论](1) HMWAPN及L/HA、L/A与儿童肥胖、MS显著关联且可以区分不同肥胖亚型(2)基因水平的研究为调节脂联素相关功能通路和新药靶点奠定了基础
[Abstract]:[objective] to investigate the relationship between serum high molecular weight adiponectin HMWAPNs, leptin / Leptinn / macromolecular adiponectin / L / HPA, leptin / adiponectin / L / A ratio and metabolic syndrome in children with metabolic syndrome (n = 2) and to explore the relationship between serum total adiponectin and serum adiponectin, and to explore the relationship between the ratio of leptin / adiponectin / adiponectin / adiponectin and metabolic syndrome in children with metabolic syndrome. Association of adiponectin and leptin / their ratio with MHO in children and adolescents.) to explore and verify the association between the polymorphism of some candidate gene loci and adiponectin level in Chinese population [methods] in 2004, children in Beijing were selected to study the relationship between the polymorphism of some candidate gene loci and adiponectin level. A total of 3 520 children aged 6 to 18 years old from the total sample of metabolic syndrome in adolescents were investigated. The diagnosis of metabolic syndrome was performed according to the revised criteria established by IDF in 2007. Elisa was used to determine the level of serum macromolecular adiponectin. The levels of total adiponectin and leptin were compared. The correlation between HAL / HAL / A and metabolic syndrome components was analyzed by variance analysis and chi-square test. The area under the operating characteristic curve was used to study the diagnostic value of L / HA and L / A in children with metabolic syndrome, and the logical regression was used to study the risk factors of MHO. Covariance and multivariate linear regression analysis of the relationship between SNP locus and serum adiponectin. The higher the detection rate of metabolic syndrome (MS): the change of macromolecule adiponectin the contrary, the more MS risk factors were found in each group. The area under the ROC curve was larger than that under the L / HA curve and the area under the adiponectin curve. The proportion of MHO in obese people was 54.71%. The ratio of total adiponectin and macromolecular adiponectin in MHO group was higher than that in MHO group, and the lower LEP and LHA level was 0.05.5) Logistic regression analysis. Reduced APN and elevated LEP were found to be independent risk factors for metabolic abnormal obesity (P0.05P0. 05). It is the first time that 5 of 7 SNP loci were found to be associated with two adiponectin levels in Chinese population, and 6 were associated with total adiponectin level. 7) among them, 6 were found to be associated with total adiponectin level for the first time. CDH13 rs4783244 is highly correlated with total adiponectin and macromolecule adiponectin levels in Chinese population. The significant levels of HMWAPN and L / HAN / L / A are 10-37-10-34 [conclusion] HMWAPN and L / HAN / L / A are significantly associated with childhood obesity. This study provides a basis for regulating adiponectin related functional pathways and new drug targets.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R723.14;R725.8

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