炎症反应、脂毒性关联脂肪细胞因子及其重要的基因SNPs与延边朝鲜族和汉族代谢综合征易感性的关系

It was considered formerly that insulin resistance (IR) was the main pathogenesis of metabolic syndrome (MS), but now many studies showed that IR was initiated by inflammatory response and fatty toxicity induced by abdominal obesity, and then MS was developed. There were significant differences in prevalence rate of IR and MS between Korean and Han nationality of Yanbian area, especially the abdominal obesity as a MS component had the most significant racial differences. 1000 cases of obese patients and 1000 cases of non-obese patients were selected in each nationality to conduct case-control study, and the adipocyte factors associated with inflammatory response and fatty toxicity were detected in the subjects, and 4 locus of single nucleotide polymorphisms (SNPs) of adiponectin gene with susceptible to MS were detected by PCR. To explore the predictive value of inflammatory response and fatty toxicity for obesity to IR and MS risks, and to study the correlation between adiponectin gene and abdominal obesity, MS in the population of Korean and Han nationality of Yanbian area and search for its specific SNPs locus, and to analyze the multiple interactive relationship between SNPs of adiponectin gene and inflammatory response, fatty toxicity relative factors and occurrence of obesity, IR and MS. This project is the first time at home and abroad in the population of Korean and Han nationality of Yanbian area to study the mechanisms of inflammatory response and fatty toxicity for MS episodes, correlation of adiponectin gene SNPs and MS, and the multiple interactive relationship of genetic factors and environmental factors on obesity, IR and MS. The results of this study will clarify the pathogenesis of MS and the cause of high incidence of MS in Yanbian Korean, and provide the reliable basis of early screening，primary prevention and treatment for MS.

过去认为IR是MS的发病机制，而目前则认为腹型肥胖诱导炎症反应、脂毒性等过程引起IR，继而发生MS。延边不同民族IR及MS患病率出现差异，且腹型肥胖作为MS的组分种族差异最为显著。对中国延边不同民族肥胖者、非肥胖者进行病例对照研究，检测该人群炎症及脂毒性相关细胞因子，采用PCR技术检测MS易感脂联素基因的4个SNPs位点。探讨炎症和脂毒性相关细胞因子对肥胖人群IR及MS风险的预测效果；探索脂联素基因在朝鲜族和汉族人群与肥胖和MS相关性，寻找其特异SNPs位点；分析脂联素基因SNPs与炎症及脂毒性相关细胞因子对肥胖、IR及MS发生的多重交互关系。本研究是国内外首次对朝鲜族和汉族肥胖人群MS发生的炎症和脂毒性机制，脂联素基因SNPs与MS相关性，以及遗传与环境因素对肥胖、IR及MS风险的多重交互关系的研究。研究结果将为阐明MS的发病机制和朝鲜族MS高发的原因，也为早期筛选及防治MS提供依据。

过去认为IR是MS的发病机制，而目前则认为腹型肥胖诱导炎症反应、脂毒性等过程引起IR，继而发生MS。延边不同民族IR及MS患病率出现差异，且腹型肥胖作为MS的组分种族差异最为显著。本研究对中国延边不同民族肥胖者、非肥胖者进行病例对照研究，检测该人群炎症及脂毒性相关细胞因子，采用PCR技术检测MS易感基因SNPs位点。探讨炎症和脂毒性相关细胞因子对肥胖人群IR及MS风险的预测效果；探索脂联素基因在朝鲜族和汉族人群与肥胖和MS相关性，寻找其特异SNPs位点。研究结果1显示：BMI、WC和HOMA-IR与不同脂肪细胞因子的关联程度有所不同，即延边地区小学生不同肥胖指标、HOMA-IR和脂肪细胞因子的分布特征出现明显的民族差异；BMI、WC和HOMA-IR与不同脂肪细胞因子的关联程度有所不同，BMI和WC与瘦素的关联程度大于HOMA-IR，HOMA-IR与脂联素和TNF-α的关联程度大于BMI和WC。研究结果2显示：本地区朝鲜族和汉族学生脂肪细胞因子和不同代谢指标的分布存在差异；脂肪细胞因子与不同代谢指标的相关性程度有所不同，且存在民族差异。研究结果3显示：1）延边地区朝鲜族和汉族学生存在NOS3基因rs3918227位点、PCK1基因rs1042531位点及ADIPOQ基因rs17846872位点具有单核苷酸多态性。2）NOS3基因rs3918227位点及ADIPOQ基因rs17846872位点基因型和等位基因频率分布特征均存在民族差异；PCK1基因rs1042531位点位只有等位基因频率分布特征存在民族差异。3）朝鲜族和汉族学生多种代谢指标与其相关基因SNPs的关联程度有所不同，且存在民族差异。研究结果4显示：延边地区学生FFA和BMI均与MS患病密切相关，而且FFA升高合并合并超重及肥胖学生显著升高MS患病危险性；FFA水平升高可以预测MS的患病危险，并且对于朝鲜族学生的预测作用强于汉族学生。本研究是国内外首次对朝鲜族和汉族肥胖人群MS发生的炎症和脂毒性机制，MS相关基因SNPs与MS相关性。研究结果将为阐明MS的发病机制和朝鲜族MS高发的原因，也为早期筛选及防治MS提供依据。