中国云南纳西族脑血管病患者载脂蛋白E基因的多态性

Currently it is not well known whether apolipoprotein E(ApoE) is a genetic susceptibility factor for cerebrovascular diseases in the Chinese Naxi population.The present study detected and sequenced ApoE polymorphisms of 90 patients with cerebrovascular diseases(58 cases of cerebral infarction and 32 cases of intracerebral hemorrhage),and 50 normal people of Naxi nationality from Yunnan province,China.The populations were used to analyze the relationship of ApoE polymorphisms with cerebral infarction and intracerebral hemorrhage.Results showed an association between ApoE gene polymorphism and the onset of cerebral infarction,and a possibility that the ε4 allele is a susceptibility locus for the risk of cerebral infarction.However,there was no evidence of a relationship between the ApoE gene polymorphism and cerebral hemorrhage.     

Carbohydrate intake, serum lipids and apolipoprotein E phenotype show association in children

Aim:  To study the association between carbohydrate intake and serum lipids in children, and influence of apolipoprotein E phenotype (apoE) on the association.
Subjects/methods:  A total of 644 children from a prospective, randomized atherosclerosis prevention trial (STRIP) participated in this longitudinal study at age 5 (n = 644), 7 (n = 585) and 9 (n = 550) years. ApoE phenotype, fasting triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol concentrations and 4-day food records were analysed.
Results:  An increase in the total carbohydrate intake by 1 E% (percentage of total daily energy intake) associated with a decrease in HDL cholesterol by 0.006 mmol/L (p < 0.001) when adjusted for saturated, monounsaturated and polyunsaturated fatty acid, age, gender, body mass index and STRIP study group. The inverse association between total carbohydrate intake and HDL cholesterol was evident in children with apoE3 (p < 0.001) or apoE4 (p < 0.001), but not in those with apoE2 (p = 0.78). An increase in total carbohydrate intake by 1 E% increased triglycerides by 0.02 mmol/L (p < 0.001) independently of apoE phenotype, while 1 E% increase in sucrose intake increased triglycerides by 0.01 mmol/L (p < 0.001).
Conclusion:  Carbohydrate intake has a relatively small effect on serum lipids in children. Children with the apoE3 or E4 but not with E2 phenotype show reduction in HDL cholesterol with increasing carbohydrate intake indicating that genetic and environmental factors interact with children's lipoprotein metabolism.     

高脂血症患者APOB／CIII／E基因多态性交互作用的研究

目的探讨原发性高脂血症载脂蛋白（Apo）B、CIII、E基因中ApoB MspI、ApoB XbaI、ApoB EcorI、ApoCIII3175、ApoCIII3206、ApoE112／158等7个位点基因多态性间的交互作用。方法采用病例一对照相关性研究策略，选择昆明地区汉族作为研究对象，用基因芯片检测技术，对91例高脂血症患者及76例健康对照者进行ApoB MspI、ApoB Xbal、ApoB EcorI、ApoCIII3175、ApoCIII3206、ApoE112／158等6个位点基因多态性进行检测。用比值比（odd ratio，OR）估计相对危险度。用MDR分析多基因相互作用。结果用MDR分析法，对昆明地区汉族高脂血症患者上述6个位点基因型多态性的基因-基因交互作用进行了分析，发现两位点MspI—E112／158、三位点MspI—CIIB206-E112／158和四位点MspI—XbaI—CIII3206-E112／158这三种模型均具有统计学意义（P〈0．001），但三位点MspI—CIII3206-E112／15模型的交叉验证一致性系数最大（10／10）为最佳模型，该模型包含了位点ApoBMspI、ApoCIII3206和ApoE112／158位点．提示这三个基因位点之间可能存在基因-基因交互作用。该模型的Odd Ratio为14．870（95％CI：1．305—169．43）。结论发现昆明地区汉族人群7个高脂血症候选基因位点中，MspI—CIII3206-E112／158三个基因多态性之间可能存在基因-基因交互作用。     

载脂蛋白E基因多态性与高脂血症痰瘀证患者血脂水平关系的研究

目的:研究载脂蛋白E(ApoE)基因多态性对高脂血症痰瘀证患者血脂水平的影响。方法:运用PCR-RFLP法检测210例高脂血症痰瘀证患者ApoE基因分型,分析ApoE基因多态性与血脂总胆固醇(TC)、甘油三酯(TG)、低密度胆固醇(LDL-C)、高密度胆固醇(HDL-C)水平的关系,结果:高脂血症痰瘀证患者不同ApoE基因型,血脂LDL-C水平,按照E3/4﹥E3/3﹥E2/3的规律逐渐降低,经比较具有显著性差异,P<0.01(P=0.0046),以E3/4为最高,E2/3为最低,而TC、TG、HDL-C水平无明显差异。结论:ApoE基因多态性影响高脂血症血脂水平,E4基因型痰瘀证个体血脂LDL-C水平明显增高,推测E4基因型可能是高脂血症痰瘀证候主要易感基因之一。     

载脂蛋白A5基因-1131T＞C多态性与回、汉族血脂相关性的研究

目的研究载脂蛋白A5基因-1131T>C多态性位点与血甘油三酯的关系。方法对226例回、汉族健康人应用聚合酶链反应-限制片多态性方法进行基因分型。结果-1131T>C的3种基因型在回、汉族人群中的分布有差异性,但稀有等位基因C的分布频率无差异性;回、汉两民族携带C等位基因的个体(TC和CC型)的TC、TG、LDL-C、APOA、ApoB水平均比非携带C等位基因(TT型)个体略高,但无显著性差异(P>0.05)。结论-1131T>C对回、汉族血脂水平影响无显著性差异,与回、汉族血脂水平无相关性。     

Immunohistochemical study of distribution of apolipoproteins E and D in human cerebral beta amyloid deposits

Several molecules are known to be closely associated with amyloid deposits in human brain. Among these, apolipoproteins such as apolipoproteins E (apo E) and J (apo J) have been found in two neuropathological hallmarks of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA): senile plaques (SPs) and cerebrovascular amyloid. These apolipoproteins may be implicated in amyloid fibrillogenesis. Apo D is a multiligand-multifunctional glycoprotein present in SPs, as we previously reported. The aim of this work is to study the link between immunolocalization of apo E and apo D in AD and CAA brains. Both apolipoproteins were found in all types of SPs, but apo E was observed more often than apo D in mature plaques. Whereas apo E is always located overlapping the amyloid core, apo D seems to situate preferably around and near the amyloid. Immunohistochemistry revealed that these apolipoproteins behave differently in cerebral vessels. Apo E labeling in vessels appears mainly linked to amyloid deposits, whereas apo D shows a distribution almost opposite to that of apo E. This could be an indication of the different roles that each apolipoprotein plays in the pathogenesis of amyloid deposition.     

Apolipoprotein E4 inhibits, and apolipoprotein E3 promotes neurite outgrowth in cultured adult mouse cortical neurons through the low-density lipoprotein receptor-related protein

The apolipoprotein E4 (apoE4) genotype is a major risk factor for Alzheimer's disease (AD); however, the mechanism is unknown. We previously demonstrated that apoE isoforms differentially modulated neurite outgrowth in embryonic neurons and in neuronal cell lines. ApoE3 increased neurite outgrowth whereas apoE4 decreased outgrowth, suggesting that apoE4 may directly affect neurons in the brain. In the present study we examined the effects of apoE on neurite outgrowth from cultured adult mouse cortical neurons to examine if adult neurons respond the same way that embryonic cells do. The results from this study demonstrated that (1) cortical neurons derived from adult apoE-gene knockout (apoE KO) mice have significantly shorter neurites than neurons from adult wild-type (WT) mice; (2) incubation of cortical neurons from adult apoE KO mice with human apoE3 increased neurite outgrowth, whereas human apoE4 decreased outgrowth in a dose-dependent fashion; (3) the isoform specific effects were abolished by incubation of the neurons with either receptor associated protein (RAP) or lactoferrin, both of which block the interaction of apoE-containing lipoproteins with the low-density lipoprotein receptor-related protein (LRP). These data suggest a potential mechanism whereby apoE4 may play a role in regenerative failure and accelerate the development of AD.     

云南省白族和汉族冠心病患者载脂蛋白E基因多态性研究

目的 探讨云南省确诊的白族和汉族冠心病（CHD）病人载脂蛋白E（ApoE）基因多态性的民族差异。方法 选择云南省确诊的冠心病病人，白族21例和汉族77例（其中80病人通过冠脉造影证实，18例病人有明确的心梗病史）。采用生物化学方法测定其血清血脂，应用聚合酶链反应-限制性片段长度多态性分析法，以Hhal内切酶及聚丙烯酰胺凝胶电泳确定ApoE基因多态性。结果 在白族CHD组和汉族CHD组均以ε3等位基因以及E3，3基因型最常见，两组之间E2／3、E3／3、E3／4基因型的分布未见统计学差异；白族组和汉族组中ε2、ε3、84等位基因频率比较无统计学差异（P〈0．05）；两组中含84等位基因携带者总胆固醇（TC）和低密度脂蛋白胆固醇和（LDL-C）显著高于其他基因型组，（P〈0．01）。结论在云南省白族和汉族人群之间ApoE基因型分布没有明显差异，白族和汉族人群中ε4等位基因是影响血清TC、LDL-C水平的重要遗传因素之一。     

载脂蛋白E基因多态性与老年期抑郁症的相关性研究

目的 探讨载脂蛋白E（ApoE）基因多态性与老年期抑郁症的关系。方法 测定60例老年期抑郁症和60例正常对照组的ApoE基因型。患者组入组时评定HAMD，治疗6周后评定疗效（HAMD减分率≥50％为有效，〈50％为无效）。结果 老年期抑郁症患者与正常对照组的ApoE的基因型和等位基因频率分布均差异无显著性（x^2分别为2．200和1．435，P分别为0．699和0．488）；按有无伴发心脑血管疾病将患者分为两组，两组的基因型和等位基因频率分布差异均无显著性（x^2分别为3．329和3．811，P分别为0．504和0．149）；按有无伴发认知功能障碍将患者分为两组，两组的基因型和等位基因频率分布差异均无显著性（x^2分别为2．640和2．010，P分别为0．620和0．366）；按治疗6周时的疗效将患者分为两组，两组的基因型分布差异无显著性（x^2=6．557，P=0．161），但两组间的等位基因频率分布差异有显著性（x^2=7．537，P：0．023）。结论 ApoE基因型可能在老年期抑郁症的发病中不起重要作用。     

Association of serum low-density lipoprotein metabolism with oestrogen receptor gene polymorphisms in healthy children

The aim of this study was to reveal the association of serum lipid and apolipoprotein levels with oestrogen receptor (ER) Xba I and Pvu II polymorphisms in 102 healthy Japanese school children (56M, 46F) aged 10-15 y. Each genotype of the genomic DNA extracted from peripheral leukocytes was determined using polymerase chain reaction and digestion with Xba I or Pvu II. The genotypes were coded as either X1 or X2 (Xba I) and P1 or P2 (Pvu II), when XI, P1 signified the absence of and X2, P2 the presence of restriction sites. The fasting serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride and apolipoproteins A1, B and E were measured. In the Xba I polymorphism, LDL cholesterol, apolipoprotein B levels of the XI/XI genotype were significantly higher than those of the others. The other lipid and apolipoprotein levels were not significantly different among the three genotypes. In the Pvu II polymorphism, there were no significant differences in serum lipids and lipoproteins among the three genotypes. This study reveals that Xba I polymorphisms are related to LDL metabolism. These findings support previous reports that the LDL-lowering effects of oestrogen occur through the ER (alpha) pathway. The Xba I polymorphism may be one of the genetic factors in the control of LDL metabolism.