血脂异常个体化健康管理关键因素的探索
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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。
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.
     Objective
     we 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.
     Methods
     In 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.
     Results
     Controllable 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.
     Recommendation
     Carring 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.
引文
[1]Who. Chronic diseases and their common risk factors [Z].2005.
    [2]Who. Rethinking diseases of affluence the economic impact of chronic diseases [Z].2005.
    [3]吴钢.健康与健康管理[J].江苏预防医学,2005(3):75-77.
    [4]中华人民共和国卫生部疾病预防控制局.中国慢性病报告[R].,2006.
    [5]卫生部新闻办公室.卫生部公布第四次国家卫生服务调查主要结果[Z].20098.
    [6]中国成人血脂异常防治指南制订联合委员会.中国成人血脂异常防治指南[J].中华心血管病杂志,2007(5):390-419.
    [7]曾碧强.饮食因素对高血脂病人血脂变化的影响[D].中山大学,2007.
    [8]张凤凤.不同阶层人群饮食行为与血脂关系的研究[D].山东大学,2010.
    [9]赵东.中国人群的血脂流行病学研究[J].中华心血管病杂志,2003,3(1):74-78.
    [10]苏蓉,于德水.高脂血症的危害及防治[J].中国当代医药,2009(8):128-129.
    [11]李健斋,牛庆田,王抒.衰老进程中血脂、脂蛋白与载脂蛋白的变化[J].中华老年医学杂志,1990,4(9):200-205.
    [12]华琦,汤哲.北京市老年人群体重、血脂、血压及血糖水平的调查与分析[J].中华内科杂志,1997(1):19-21.
    [13]张培珍.血脂异常的中老年人调脂运动处方的研究[D].北京体育大学,2004.
    [14]谢友红,王永红.健康管理的价值初探[J].现代预防医学,2008(1):110-111.
    []5]黄建始.美国的健康管理:源自无法遏制的医疗费用增长[J].中华医学杂志,2006(15):1011-1013.
    [16]李星.构建适合中国国情的冠心病健康管理模式[D].南京医科大学,2010.
    [17]巴德年.“3P”医学[Z].北京:2006.
    [18]Knoblauch H, Bauerfeind A, Toliat M R, et al. Haplotypes and SNPs in 13 lipid-relevant genes explain most of the genetic variance in high-density lipoprotein and low-density lipoprotein cholesterol [J]. Hum Mol Genet,2004,13(10):993-1004.
    [19]Kathiresan S, Willer C J, Peloso G M, et al. Common variants at 30 loci contribute to polygenic dyslipidemia [J]. Nat Genet,2009,41 (1):56-65.
    [20]Aulchenko Y S, Ripatti S, Lindqvi st I, et al. Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts[J]. Nat Genet,2009,41(1):47-55.
    [21]Sabatti C, Service S K, Hartikainen A L, et al. Genome-wide association analysis of metabolic traits in a birth cohort from a founder population [J]. Nat Genet,2009,41(1):35-46.
    [22]Kathiresan S, Melander 0, Guiducci C, et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans [J]. Nat Genet,2008,40(2):189-197.
    [23]Willer C J, Sanna S, Jackson A U, et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease[J]. Nat Genet,2008,40 (2):161-169.
    [24]Hegele R A, Ban M R, Hsueh N, et al. A polygenic basis for four classical Fredrickson hyperlipoproteinemia phenotypes that are characterized by hypertriglyceridemia[J]. Hum Mol Genet,2009,18 (21):4189-4194.
    [25]Wang J, Ban M R, Zou G Y, et al. Polygenic determinants of severe hypertriglyceridemia[J]. Hum Mol Genet,2008,17 (18):2894-2899.
    [26]Liu Y, Zhou D, Zhang Z, et al. Effects of genetic variants on lipid parameters and dyslipidemia in a Chinese population[J]. J Lipid Res,2011,52 (2):354-360.
    [27]Pan L A, Chen Y C, Huang H, et al. G771C Polymorphism in the MLXIPL Gene Is Associated with a Risk of Coronary Artery Disease in the Chinese: A Case-Control Study[J]. Cardiology,2009,114 (3):174-178.
    [28]Kathiresan S, Melander 0, Anevski D, et al. Polymorphisms associated with cholesterol and risk of cardiovascular events [J]. N Engl J Med,2008,358(12):1240-1249.
    [29]王琼,张青云,刘娟.北京地区13336例成人空腹血脂水平分析[J].中华检验医学杂志,2007,30(5):524-528.
    [30]庞金荣,颜中.西藏高原地区藏族人群血脂水平分析[J].中华检验医学杂志,2010,33(9):856-861.
    [31]Ockene I S, Miller N H. Cigarette smoking, cardiovascular disease, and stroke: a statement for healthcare professionals from the American Heart Association. American Heart Association Task Force on Risk Reduction[J]. Circulation,1997,96(9):3243-3247.
    [32]Freedman D S, Srinivasan S R, Shear C L, et al. Cigarette smoking initiation and longitudinal changes in serum lipids and lipoproteins in early adulthood: the Bogalusa Heart Study [J]. Am J Epidemiol,1986,124 (2):207-219.
    [33]潘兴强,刘永跃,张显玉,等.基于多因子降维法模型的醛固酮合成酶基因多态性与饮酒指数对蒙古族人群高血压的交互作用[J].中流行病学杂志,2009,30(9):955-959.
    [34]张林峰,赵连成,周北凡,等.男性饮酒与缺血性脑卒中发病关系的研究[J].中华流行病学杂志,2004(11).
    [35]陈理声,姚洪章,钟福华,等.城市中老年居民血脂异常影响因素研究[J].疾病控制杂志,2006(5):485-488.
    [36]戴秀英,孔凡元,刘天锡.血脂过多者诸种饮食因素研究:205例配对调查[J].宁夏医学杂志,1990(3):145-146.
    [37]邓娟,曾碧强,陈裕明,等.蔬菜、水果及大豆食物对高血脂病人血脂的影响[J].营养学报,2009(5).
    [38]Gorinstein S, Caspi A, Libman I, et al. Preventive effects of diets supplemented with sweetie fruits in hypercholesterolemic patients suffering from coronary artery disease [J]. Prev Med,2004,38(6):841-847.
    [39]潘星月,董幼丹,杨洪梅,等.沈阳市某社区中老年人血脂及相关行为危险因素现况调查[J].中国初级卫生保健,2010(4).
    [40]张忠英.运动减肥对肥胖儿童少年脂蛋白脂酶活性和血脂影响的研究[D].上海体育学院,2010.
    [41]许汪宇,陈文鹤,沈勋章.中低强度有氧运动结合饮食控制对肥胖青少年血脂和肝脏功能的影响[J].中国运动医学杂志,2011(8):706-711.
    [42]吴静娜,卢建华,王福影,等.论健康管理的历史和现实[J].医学与社会,2008(7):31-32.
    [43]Jansen A C, van Aalst-Cohen E S, Tanck M W, et al. The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients [J]. J Intern Med,2004,256 (6):482-490.
    [44]张明华,叶平.饮酒与血脂代谢异常研究进展[J].心血管病学进展,2010(3):370-373.
    [45]Halbert J A, Silagy C A, Finucane P, et al. Exercise training and blood lipids in hyperlipidemic and normolipidemic adults:a meta-analysis of randomized, controlled trials[J]. Eur J Clin Nutr,1999,53(7):514-522.
    [46]杨中荣,蒋善群,秦献辉,等.安庆农村社区高血压人群血脂与年龄的相关性[J].安徽医科大学学报,2010(4).
    [47]李立明,饶克勤,孔灵芝,等.中国居民2002年营养与健康状况调查[J].中华流行病学杂志,2005(7):478-484.
    [48]科技攻关课题协作组国家九五.我国中年人群心血管病主要危险因素流行现状及从80年代初至90年代末的变化趋势[J].中华心血管病杂志,2001,29(1):74-79.
    [49]张晓媚.广州市某社区老年人血脂与年龄、性别的关系分析[J].国际医药卫生导报,2011,17(3):380-381.
    [50]何立芸,郭丽君. 女性血脂代谢特点及处理[J].临床荟萃,2006(23):1689-1691.
    [51]Am S, M S, B M, et al. Lipids and lipoproteins in women [J]. HERZ,2005,30(5):368-374.
    [52]Connelly P W, Stachenko S, Maclean D R, et al. The prevalence of hyperlipidemia in women and its association with use of oral contraceptives, sex hormone replacement therapy and nonlipid coronary artery disease risk factors. Canadian Heart Health Surveys Research Group [J]. Can J Cardiol,1999,15 (4):419-427.
    [53]茅旭,王岩,田雅玲.正常人奶油摄入量与血脂水平的剂量效应关系[J].解放军预防医学杂志,1993(4):300-301.
    [54]Lichtenstein A H, Jauhiainen M, Mcgladdery S, et al. Impact of hydrogenated fat on high density lipoprotein subfractions and metabolism [J]. J Lipid Res,2001,42 (4):597-604.
    [55]Clevidence B A, Judd J T, Schaefer E J, et al. Plasma lipoprotein (a) levels in men and women consuming diets enriched in saturated, cis-, or trans-monounsaturated fatty acids [J]. Arterioscler Thromb Vasc Biol,1997,17(9):1657-1661.
    [56]Hung H C, Joshipura K J, Jiang R, et al. Fruit and vegetable intake and risk of major chronic disease [J]. J Natl Cancer Inst,2004,96(21):1577-1584.
    [57]Crouse S F, O'Brien B C, Rohack J J, et al. Changes in serum lipids and apolipoproteins after exercise in men with high cholesterol:influence of intensity[J]. J Appl Physiol,1995,79 (1):279-286.
    [58]许豪文.运动生物化学概论[M].北京:高等教育出版社,2001.
    [59]Halbert. Exercise training and blood lipids in hyperlipidemic and normolipidemic adults:a meta-analysis of randomized, controlled trials [J]. Eur J Clin Nutr,1999,53(7):514-522.
    [60]Qin L, Sun L, Ye L, et al. A case-control study between the gene polymorphisms of polyunsaturated fatty acids metabolic rate-limiting enzymes and coronary artery disease in a Chinese Han population[J]. Prostaglandins Leukot Essent Fatty Acids,2011,85 (6):329-333.
    [61]Park M H, Kim N, Lee J Y, et al. Genetic loci associated with lipid concentrations and cardiovascular risk factors in the Korean population[J]. J Med Genet,2011,48(1):10-15.
    [62]A genome-wide perspective of genetic variation in human metabolism[J].
    [63]Nakayama K, Bayasgalan T, Tazoe F, et al. A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle[J]. Hum Genet,2010,127 (6):685-690.
    [64]刘婉莹.广西白裤瑶族人群内皮脂肪酶基因多态性与血脂水平的关系[D].广西医科大学,2011.
    [65]Wan-Ying L, Rui-Xing Y, Lin Z, et al. Association of the LIPG 584C>T polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations[Z]中国广东广州:2011156-157.
    [66]Jeemon P, Pettigrew K, Sainsbury C, et al. Implications of discoveries from genome-wide association studies in current cardiovascular practice [J]. World Journal of Cardiology,2011 (7):230-247.
    [67]何颖.吸烟与血脂因素和冠心病的关系[J].检验医学与临床,2007(12):1191-1192.
    [68]高倩,逢增昌,吴义丽.吸烟对青岛地区城乡居民血脂水平影响的研究[J].预防医学论坛,2011(5):385-387.
    [69]H. M. F. Farin F A S H. The relationship between insulin resistance and dyslipidaemia in cigarette smokers [J].2006.
    [70]钟毓瑜,马静,陈志锦,等.吸烟与中年男性血脂及氧化低密度脂蛋白的关系[J].广东医学,2005(9).
    [71]吴伟娥,张红英,张程赪.团体戒酒活动对酒依赖患者应对方式和社会支持的影响[J].中国民康医学,2011(5):618-619.
    [72]周莉.中国汉族人群血脂水平及冠心病的遗传易感性研究[D].华中科技大学,2011.
    [73]倪国贞,朱铁兵,李瑞洁,等.ABCA1基因R1587K位点多态性与冠心病及血脂水平的关系[J].南京医科大学学报(自然科学版),2008(8).
    [74]王禾,赵泽霖.冬泳锻炼对老年人血脂、心功能的影响[J].沈阳体育学院学报,2011(1).
    [75]谢娟,来则民,黄国伟,等.高脂血症危险因素研究[J].疾病控制杂志,2000(1):64-66.
    [76]焦溥蕙.冠心病的预防策略[J].中国老年学杂志,2005(7):860-863.
    [77]Liu J, Hong Y, D' Agostino R S, et al. Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-Provincial Cohort Study [J]. JAMA,2004,291 (21):2591-2599.
    [78]中国营养学会.中国居民膳食指南[R].,2007.
    [79]朱庆芳.我国老龄化社会的特点、问题和对策[Z].2004:2012.
    [1]中国成人血脂异常防治指南制订联合委员会.中国成人血脂异常防治指南[J].中华心血管病杂志,2007(5):390-419.
    [2]武阳丰,周北凡,李莹,等.我国中年人群心血管病主要危险因素流行现状及从80年代初至90年代末的变化趋势[J].中华心血管病杂志,2001,29(2):74-79.
    [3]张凤凤.不同阶层人群饮食行为与血脂关系的研究[D].山东大学,2010.
    [4]赵东.中国人群的血脂流行病学研究[J].中华心血管病杂志,2003,3(1):74-78.
    [5]Jeppesen J, Hein H 0, Suadicani P, et al. Triglyceride concentration and ischemic heart disease: an eight-year follow-up in the Copenhagen Male Study [J]. Circulation,1998,97(11):1029-1036.
    [6]Hokanson J E, Austin M A. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level:a meta-analysis of population-based prospective studies [J]. J Cardiovasc Risk,1996,3(2):213-219.
    [7]王薇,赵冬,吴兆苏,等.中国11省市35~64岁人群血清甘油三酯分布特点及与其他心血管病危险因素关系的研究[J].中华流行病学杂志,2001,22(1):26-29.
    [8]刘静,赵冬,秦兰萍,等.低密度脂蛋白胆固醇与心血管病发病关系的前瞻性研究[J].中华心血管病杂志,2001(9).
    [9]李莹,陈志红,周北凡,等.血脂和脂蛋白水平对我国中年人群缺血性心血管病事件的预测作用[J].中华心血管病杂志,2004(7).
    [10]贾跃胜,邓春波,袁世宏.ApoE基因多态性及其对血脂、冠心病发病年龄及冠脉狭窄程度的影响[J].山西职工医学院学报,2001(3):53-55.
    [11]马陈福,白新胜.804例血脂水平与血压、年龄、性别的相关性研究[J].福建医药杂志,2003,25(6):63-64.
    [12]毕小云,邓小玲,肖琴,等.吸烟对血脂的影响[J].重庆医科大学学报,2004(1).
    [13]Jansen A C, van Aalst-Cohen E S, Tanck M W, et al. The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients [J]. J Intern Med,2004,256 (6):482-490.
    [14]刘扬,赵莉.饮酒对血脂的影响及与脑血管病的关系[J].吉林医学,2008(21):1885-1886.
    [15]张明华,叶平.饮酒与血脂代谢异常研究进展[J].心血管病学进展,2010(3):370-373.
    [16]邓娟,曾碧强,陈裕明,等.蔬菜、水果及大豆食物对高血脂病人血脂的影响[J].营养学报,2009(5).
    [17]刘迎利.饮食因素及ApoE基因多态性与血脂水平相关研究[D].陕西师范大学,2005.
    [18]宋法明.有氧运动对中老年高血脂患者的血脂水平影响研究[J].现代预防医学,2011(11):2098-2099.
    [19]Lee H, Park J E, Choi I, et al. Enhanced functional and structural properties of high-density lipoproteins from runners and wrestlers compared to throwers and lifters [J]. BMB Rep,2009,42 (9):605-610.
    [20]Halbert J A, Silagy C A, Finucane P, et al. Exercise training and blood lipids in hyperlipidemic and normolipidemic adults:a meta-analysis of randomized, controlled trials [J]. Eur J Clin Nutr,1999,53(7):514-522.
    [21]Frazer K A, Ballinger D G, Cox D R, et al. A second generation human haplotype map of over 3.1 million SNPs[J]. Nature,2007,449 (7164):851-861.
    [22]Kathiresan S, Willer C J, Peloso G M, et al. Common variants at 30 loci contribute to polygenic dyslipidemia [J]. Nat Genet,2009,41(1):56-65.
    [23]Willer C J, Sanna S, Jackson A U, et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease [J]. Nat Genet,2008,40 (2):161-169.
    [24]Sabatti C, Service S K, Hartikainen A L, et al. Genome-wide association analysis of metabolic traits in a birth cohort from a founder population [J]. Nat Genet,2009,41(1):35-46.
    [25]Wang J, Ban M R, Zou G Y, et al. Polygenic determinants of severe hypertriglyceridemia[J]. Hum Mol Genet,2008,17 (18):2894-2899.
    [26]Liu Y, Zhou D, Zhang Z, et al. Effects of genetic variants on lipid parameters and dyslipidemia in a Chinese population [J]. J Lipid Res,2011,52(2):354-360.
    [27]Kathiresan S, Melander 0, Guiducci C, et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans [J]. Nat Genet,2008,40(2):189-197.
    [28]孟康,吕树铮,王绿娅,等.高脂血症患者载脂蛋白B基因3‘端可变数目串联重复序列基因与血脂水平的关系[J].中华老年医学杂志,2006,25(6):424-427.
    [29]陈筱潮,徐明彤,韩春丽,等.中国汉族人载脂蛋白B基因多态性与冠心病关系的Meta分析[J].中华医学遗传学杂志,2006(6).
    [30]杨爱红,宋达琳,孙黎明.载脂蛋白E增强子基因多态性在冠心病与2型糖尿病患者之间的比较[J].齐鲁医学检验,2004(6).
    [31]张典文,崔国方,王刚,等.载脂蛋白E基因多态性、内含子1基因多态性与血脂代谢关系的研究[J].中国心血管病研究杂志,2005(9).
    [32]Hj M, Rg K, G A. Apolipoprotein E polymorphism and coronary artery disease[J]. Arteriosclerosis Thrombosis And Vascular Biology,1983,3(4):310-315.
    [33]Dallongeville J, Lussier-Cacan S, Davignon J. Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis[J]. J Lipid Res,1992,33(4):447-454.
    [34]Sing C F, Davignon J. Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation [J]. Am J Hum Genet,1985,37 (2):268-285.
    [35]E B W, Visvikiss, D W. The use of measured genotype information in the analysis of quantitative phenotypes in man. II. The role of the apolipoprotein E polymorphism in determining levels, variability, and covariability of cholesterol, betalipoprotein, and triglycerides in a sample of unrelated individuals [J]. Am J Med Genet,1987,3 (27):567-582.
    [36]李国平,陈保生,薛红,等.载脂蛋白C3基因多态性-482C>T与血浆脂质的关系[J].中国动脉硬化杂志,2005(3):335-339.
    [37]钱净,胡大春,赵晓丽,等.载脂蛋白CⅢ基因多态性频率分布及与高脂血症患者关系的研究[J].中国前沿医学,2010,5(5):1-2.
    [38]郭志刚,王琦光,赖文岩,等.新发现的中国人ATP结合盒转运子A1基因M233V单核苷酸多态性及其家系调查[J].中华心血管病杂志,2006,34(12):1101-1104.
    [39]Lutucuta S, Ballantyne C M, Elghannam H, et al. Novel polymorphisms in promoter region of atp binding cassette transporter gene and plasma lipids, severity, progression, and regression of coronary atherosclerosis and response to therapy[J]. Circ Res,2001,88 (9):969-973.
    [40]Mcneish J, Aiello R J, Guyot D, et al. High density lipoprotein deficiency and foam cell accumulation in mice with targeted disruption of ATP-binding cassette transporter-1 [J]. Proc Natl Acad Sci U S A,2000,97(8):4245-4250.
    [41]Orso E, Broccardo C, Kaminski W E, et al. Transport of lipids from golgi to plasma membrane is defective in tangier disease patients and Abel-deficient mice[J]. Nat Genet,2000,24 (2):192-196.
    [42]孙琳,陈璐璐,耿厚法,等.LPL基因多态性与2型糖尿病合并脑血管病变及血脂的关系[J].山东大学学报(医学版),2009(8).
    [43]蔡庆,刘红巾,陈涛.飞行员脂蛋白脂酶基因Ser447Ter位点多态性及与血脂水平的关系[J].临床军医杂志,2011(2):209-211.
    [44]龙石银,张蓉,田英,等.肥胖者高密度脂蛋白亚类组成与脂蛋白酯酶基因多态性的关系[J].中国动脉硬化杂志,2006(2).

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