【作者】 孟强；

【导师】 杨磊； 许亮文；

【作者基本信息】 杭州师范大学 ， 社会医学与卫生事业管理， 2012， 硕士

【摘要】 血脂是指血浆中的中性脂肪(胆固醇、甘油三酯)和类脂(如磷脂)的总称。高脂血症是一种或多种脂质含量超过正常高值的病症,高脂血症的严格定义应该为血脂异常,以总胆固醇、甘油三脂增高、高密度脂蛋白胆固醇降低和(或)低密度脂蛋白胆固醇水平增高为主要特征。随着我国改革开放和经济发展,人民生活水平不断提高,社会生活方式和人口结构都发生较大改变,社会老龄化带来了前所未有的巨大挑战,血脂异常在中老年人群中具有较高的发病率,且呈现具有逐年升高的趋势,已经成为严重危害中老年人生命健康的慢性非传染性疾病。健康管理是对个体和群体身体、心理、社会适应方面的监测、评估、和干预,减少健康危险因素对健康的损害,预防疾病,改善健康。但是,其尚不能回答可控因素(生活行为)和不可控因素(生物遗传)对血脂异常贡献大小以及防控血脂异常的个体化健康管理策略与措施等。因此,利用现代“4P”医学的理念,为血脂异常个体化健康管理的全人群策略和高危人群策略提供一条节约卫生资源、降低健康维持成本、最大程度的获得人群健康的准确、持续、有效、个性化的新途径,对于维护公众健康和促进健康管理事业的发展具有重要的现实意义。研究目的通过对杭州市某社区体检中心参加健康体检的中老年人群进行全面的生活行为方式的调查,并结合其遗传基因SNP位点分型、血脂四项指标和个人一般情况等信息,分析生活行为因素和基因遗传因素对血脂总体水平的决定大小程度,并筛选出影响单项血脂水平最重要的生活行为因素和遗传基因位点的影响因素组合,为血脂异常个体化健康管理的全人群策略和重点人群策略提供新的途径。研究方法本次研究以杭州市某社区体检中心2010年3月-6月份参加体检的40岁以上中老年人为研究对象,采用现场调查的方法,对其进行问卷调查和血样采集美,并在实验室中检测基因位点分型。符合纳入标准的调查对象共490人。采用典则相关分析方法,分析生活行为方式和遗传基因SNP位点与血脂水平之间的相关关系及对血脂总体水平的决定大小程度；采用多重线性回归方法,分别筛选出影响总胆固醇、甘油三酯、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇水平的最重要的生活行为因素和遗传基因位点的影响因素组合。研究结果从总体上看,可以控制的“生活行为因素”决定男性和女性人群血脂总体水平变化的43.99%和46.87%；不可控的“基因遗传因素”决定男性和女性人群四项血脂总体水平变化的22.40%和19.88%,“年龄因素”决定男性和女性人群四项血脂总体水平变化的26.63%和12.04%。从单项血脂水平上看,血清总胆固醇水平的影响因素中,生活行为方式因素：奶油蛋糕食用量过多是男性TC水平的主要危险因素；每周参与体育锻炼3次以上、每日蔬菜食用量大于400克是女性TC水平的主要保护因素。生物遗传因素：rs174547的CC亚型是男性TC水平的主要危险因素但却是女性TC水平的主要保护因素rs2156552的TT亚型是女性TC水平的主要危险因素。血清甘油三酯水平的影响因素中,生活行为方式因素：吸烟、奶油蛋糕食用量过多是男性TG水平的主要危险因素；饮酒是女性TG水平的主要危险因素,每次锻炼时间大于30分钟是女性TG水平的主要保护因素。生物遗传因素：rs4420638的GG亚型和rs10885393的CC亚型是男性TG水平的主要危险因素；rs1800588的TT亚型和rs17145738的TT亚型是女性TG水平的主要危险因素,rs2156552的TT亚型和rs2230806的AA亚型是女性TG水平的主要保护因素。血清低密度脂蛋白胆固醇水平的影响因素中,生活行为方式因素：每日蔬菜食用量大于500g是男性LDL-C水平的主要保护因素；每周身体锻炼次数大于等于3次是女性LDL-C水平的主要保护因素,油炸食品食用过多是女性LDL-C水平的主要危险因素。生物遗传因素：rs662的AA亚型和rs3764261的TT亚型是男性LDL-C水平的主要危险因素；rs174547的CC亚型和rs515135的AA亚型是女性LDL-C水平的主要危险因素,rs2230806的AA亚型和rs10889353的CC亚型是女性LDL-C水平的主要保护因素。血清高密度脂蛋白胆固醇水平的影响因素中,生活行为方式因素：每周身体锻炼3～5次是男性HDL-C水平的主要保护因素,同时也是女性HDL-C水平的主要保护因素。生物遗传因素：rs2230806的AA亚型是男性HDL-C水平的主要保护因素；rs4846914的AA亚型是女性HDL-C水平的主要保护因素,而rs4420638的GG亚型是女性HDL-C水平的主要危险因素。建议积极开展血脂异常等慢性病防治工作、对中老年人群进行连续、有效、经济、方便、综合、连续的健康管理,预防和控制慢性病的发生与发展,为老年社会的到来做好准备。在公共卫生系统的基础上,实施一、二、三级预防相结合的策略、健康促进和健康教育并举的健康管理方式,结合生物遗传信息,确定并针对血脂异常的主要可控生活行为危险因素,实施综合防治,落实干预措施。全面预防与重点监测的点面结合,利用影响单项血脂水平变化的关键点信息,在生物遗传的基因信息指导下,做好重点人群的个体化健康管理工作,对于提高生活质量、减少疾病负担、延长健康期望寿命具有不可替代的作用。更多还原

【Abstract】 Plasma lipids refers to all lipids in plasma, it is so called hyperlipemia in the case of the total lipids or part of them go beyond the limit level, and the formal definition is the plasma lipid in abnormity or disorder, i.e. the plasma lipid levels exceed the normal limits. It consists of the serum TC level and TG level and LDL-C level go up, and HDL-C level reduce. With people’s living standard increasing, urbanizaion and industrialization, socio demographic and lifestyle have changed greatly, so the middle and old age people’s plasma lipids level is becoming higher. Health management were carried out for the middle and old age people in order to monitor, and analysis their risk of chronic disease completely, appraisal their condition of health, and guide their change the unhealthy lifestyle. With the concept of health management, the paper tries to find how to carry out prevention and control of dyslipidemia, explore effective health management system for dyslipidemia, in order to reduce morbidity and mortality of dyslipidemia, lower health care costs, improve nation health conditions. Meanwhile, the paper also has an important reference to the health management of other infectious diseases.Objectivewe analyzed the status of dyslipidemia in general population in a community hospital of Hangzhou trying to find out the reasons and the relationship between living behavior pattern and SNP and dyslipidemia and to find out preventive methods and to provide with rational lifestyle.MethodsIn this study, people aged above40years from a community hospital of Hangzhou were investigated by field survey with questionnaire survey, lifestyle survey and physical examination.497people were included. Statistic data was processed with SPSS13.0software. Canonical correlation analysis (CCA) is a statistical method that can reduce the number of tests by using multiple phenotypes and genotypes in each test. CCA compares two sets of variables (in this case, a set of living behavior pattern and SNP genotypes and a set of lipid levels) to assess the correlation between them. Beside CCA, the effects of living behavior pattern and SNPs variables on each lipid indicators were also calculated by multiple linear regression analyses.ResultsControllable living behavioral factors can determine the level of plasma lipids in male and female population of43.99%and46.87%, respectively. Uncontrollable genetic factors determine the level of plasma lipids in male and female population22.40%and19.88%, respectively. Age factors determine the level of plasma lipids in male and female population22.40%and19.88%, respectively.The factors which had statistical significance for change of TC were physical exercise, intake of vegetable, cream cake, rs174547and rs2156552. When intake of cream cake raised from0/w to5/w, the genotypes of rs174547changed from TT to CC, the male are in higher risk of hypercholesterolemia. When intake of cream cake raised from0/w to5/w, the genotypes of rs174547changed from TT to CC, the male are in higher risk of hypercholesterolemia. When physical exercise more than three times a week, intake of vegetable raised from0～399g/d to400～500g/d, the genotypes of rs174547changed from TT to CC, the female are in lower risk of hypercholesterolemia. But, when the genotypes of rs2156552changed from AA to TT, the female are in higher risk of hypercholesterolemia. The factors which had statistical significance for change of TG were smoking, drinking, physical exercise, intake of cream cake, rs4420638, rs10889353, rs1800588. rs17145738, rs2156552and rs2230806. When smoking, intake of cream cake raised from0/w to5/w, the genotypes of rs4420638changed from AA to GG, rs10889353changed from AA to CC, the male are in higher risk of hypertriglyceridemia. When drinking, the genotypes of rs1800588changed from CC to TT, rs17154738changed from CC to TT, the female are in higher risk of hypertriglyceridemia. When physical exercise more than30minutes one time, the genotypes of rs2156552changed from AA to TT, rs2230806changed from GG to AA, the female are in lower risk of hypertriglyceridemia. The factors which had statistical significance for change of LDL were physical exercise, intake of vegetable, fried foods, rs662, rs3764261, rs174547, rs515135, rs2230806and rs10885393. When intake of vegetable raised from0～399g/d to500g/d, the male are in lower risk of high low-density lipoprotein cholesterol. But, when the genotypes of rs662changed from GG to AA, rs17154738changed from GG to TT, the male are in higher risk of high low-density lipoprotein cholesterol. When physical exercise more than three times a week, the genotypes of rs2230806changed from GG to AA, rs10889353changed from AA to CC, the female are in lower risk of high low-density lipoprotein cholesterol. However, when intake of fried foods raised from0/w to1～4/w, the genotypes of rs174547changed from TT to CC, rs515135changed from GG to AA, the female are in higher risk of high low-density lipoprotein cholesterol.The factors which had statistical significance for change of HDL were physical exercise, rs4846914, rs2230806and rs4420638. When physical exercise three to five times a week, people are in lower risk of low high-density lipoprotein cholesterol. When the genotypes of rs2230806changed from GG to AA, the male are in lower risk of low high-density lipoprotein cholesterol. When the genotypes of rs4846914changed from GG to AA, the female are in lower risk of low high-density lipoprotein cholesterol. When the genotypes of rs4420638changed from AA to GG, the female are in lower risk of low high-density lipoprotein cholesterol.RecommendationCarring out the continuous, effective, economic, convenient, comprehensive, continuous health management in the elderly population, actively, to prevent chronic diseases; Developing the "three class prevention" of dyslipidemia; establish and perfect the comprehensive prevention and treatment net of dyslipidemia; Combianing of the population-based prevention strategy and high-risk prevention strategy. People should establish a correct concept of health and disease prevention. The happening and developing of hyperlipidemia is comprehensive affecting result of lifestyle and genetic factors. Hyperlipidemia will be prevented or controlled if prophylactic measure being took as early as possible. We should quit smoking habit, moderate drinking, establish good eating habits, keep exercise.更多还原