The cholesterol-raising effect of coffee in the Syrian hamster.

Adult male Syrian hamsters were fed on a high-fat diet with or without access to boiled coffee. Plasma total, low-density-lipoprotein- and high-density-lipoprotein-cholesterol and triacylglycerol concentrations were increased by the coffee and very-low-density-lipoprotein-cholesterol concentrations were lowered. It is concluded that the Syrian hamster is a suitable animal model in which to study the hypercholesterolaemic effect of coffee.     

The cholesterol-raising factor from coffee beans.

Coffee beans and some types of coffee brew-not the regular types of coffee prepared with a paper filter or with soluble coffee granules-contain the diterpenes cafestol and kahweol. Cafestol and kahweol raise the serum concentration of cholesterol and triglycerides in humans, and they also appear mildly to affect the integrity of liver cells. Both effects are transient after withdrawal of the diterpenes, and it is as yet unsure whether these effects are associated. Patients at increased risk of heart disease who drink large amounts of coffee should be advised to select brews low in diterpenes.     

Negligible amounts of cholesterol-raising diterpenes in coffee made with coffee pads in comparison with unfiltered coffee

OBJECTIVE: To determine the amounts of the serum-cholesterol raising diterpenes cafestol and kahweol in coffee made with coffee pads and the Senseo coffee machine as opposed to filtered and unfiltered coffee. DESIGN: Observational. METHOD: In five cities in the Netherlands coffee was purchased in three major supermarkets resulting in a total of 30 samples of coffee pads. The levels of cafestol and kahweol were determined by gas chromatography. As controls, the diterpene levels in filtered and unfiltered coffee were also measured. RESULTS: Coffee prepared using coffee pads contained on average 0.76 mg/l cafestol (95% CI: 0.69-0.82) and 0.85 mg/l kahweol (95% CI: 0.77-0.94). Filtered coffee contained 0.76 mg/l cafestol (95% CI: 0.63-0.88) and 0.81 mg/l kahweol (95% CI: 0.63-0.99). Unfiltered coffee contained 72.5 mg/l cafestol (95% CI: 48.5-96.4) and 71.5 mg/l kahweol (95% CI: 45.0-98.1). CONCLUSION: Coffee prepared using coffee pads and the Senseo coffee machine contained minute levels of diterpenes comparable to those of filtered coffee. Its effect on serum-cholesterol levels is therefore likely to be negligible.     

Obesity and alcohol modulate the effect of apolipoprotein E polymorphism on lipids and insulin

OBJECTIVE: To assess the interaction between apolipoprotein (apo) E polymorphism, alcohol consumption, and BMI on insulin, lipid, and lipoprotein levels in men. RESEARCH METHODS AND PROCEDURES: Cross-sectional study of 266 healthy men without hypolipidemic or antidiabetic drug treatment. BMI, apo E polymorphisms, insulin, and lipid and lipoprotein levels were assessed. Alcohol consumption was assessed by questionnaire. epsilon2/epsilon4 carriers were excluded from the analysis. RESULTS: On bivariate analysis, epsilon2 carriers had lower levels of total and low-density lipoprotein cholesterol and higher levels of apo E and lipoparticle B:E than epsilon3 carriers, the opposite being found for epsilon4 carriers compared with epsilon3 carriers; epsilon4 carriers also had significantly higher insulin levels. On multivariate analysis, significant interactions (p < 0.04) between apo E alleles and increased BMI were found for total and low-density lipoprotein cholesterol and insulin levels, the increase in those parameters with BMI being stronger among epsilon4 carriers than among epsilon3 or epsilon2 carriers. Significant interactions (p < 0.02) between apo E alleles and alcohol consumption were also found for apo B levels, which increased in epsilon2 carriers but remained relatively stable in epsilon3 and tended to decrease in epsilon4 carriers. DISCUSSION: These data suggest that effects of apo E alleles on lipids and insulin levels are partly dependent on environmental variables such as BMI and alcohol intake. These findings highlight the importance of gene x environment interactions on the deleterious effect of obesity on cardiovascular risk factors.     

Validity of animal models for the cholesterol-raising effects of coffee diterpenes in human subjects

Cafestol and kahweol, coffee lipids present in unfiltered coffee brews, potently increase LDL-cholesterol concentration in human subjects. We searched for an animal species in which cafestol similarly increases LDL-cholesterol. Such an animal model could be used subsequently as a model to study the mechanism of action of cafestol and kahweol. Cafestol and kahweol increased serum lipids in African green monkeys (Cercopithecus aethiops), cebus (Cebus apella) and rhesus (Macaca mulatta) monkeys, hamsters, rats and gerbils differently from the increase in human subjects. In African green monkeys, the rise in total cholesterol was less pronounced than that in human subjects. In addition, the increase in total cholesterol was predominantly due to a rise in HDL-cholesterol rather than LDL-cholesterol. Thus, the rise in plasma lipids might illustrate the mechanism in these monkeys rather than the mechanism in human subjects. In other animal species, cafestol and kahweol did not raise cholesterol consistently. The variability in effects on serum lipids could not be explained by the mode of administration or dose of diterpenes, nor by the amount of cholesterol in the diet. In conclusion, we did not find an animal model in which cafestol and kahweol elevate plasma lipoproteins to the same extent as in human subjects. For the time being, therefore, studies on the mechanism of action should be done preferably in human subjects.     

LDL cholesterol-raising effect of low-dose docosahexaenoic acid in middle-aged men and women

BACKGROUND: Long-chain n-3 polyunsaturated fatty acids have variable effects on LDL cholesterol, and the effects of docosahexaenoic acid (DHA) are uncertain. OBJECTIVE: The objective of the study was to determine the effect on blood lipids of a daily intake of 0.7 g DHA as triacylglycerol in middle-aged men and women. DESIGN: Men and women aged 40-65 y (n = 38) underwent a double-blind, randomized, placebo-controlled, crossover trial of treatment with 0.7 g DHA/d for 3 mo. RESULTS: DHA supplementation increased the DHA concentration in plasma by 76% (P < 0.0001) and the proportion in erythrocyte lipids by 58% (P < 0.0001). Values for serum total cholesterol, LDL cholesterol, and plasma apolipoprotein B concentrations were 4.2% (0.22 mmol/L; P = 0.04), 7.1% (0.23 mmol/L; P = 0.004), and 3.4% (P = 0.03) higher, respectively, with DHA treatment than with placebo. In addition, the LDL cholesterol:apolipoprotein B ratio was 3.1% higher with DHA treatment than with placebo (P = 0.04), which suggested an increase in LDL size. Plasma lathosterol and plant sterol concentrations were unaffected by treatment. CONCLUSION: A daily intake of approximately 0.7 g DHA increases LDL cholesterol by 7% in middle-aged men and women. It is suggested that DHA down-regulates the expression of the LDL receptor.     

ApoE基因多态性与多因素作用致冠心病研究

目的 探讨冠心病的主要危险因素及载脂蛋白E(ApoE)基因多态性与其它各危险因素之间的交互效应。方法 选择90例冠心病患者(CHD组)及90例非冠心病患者(对照组)，在Logistic回归分析的基础上，分析各因素的比值比以及ApoE基因多态性与其它危险因素之间的交互作用。结果 多因素Logistic回归结果显示，高血压史、高血脂史、肺炎衣原体(Cpn)感染、巨细胞病毒(CMV)感染和ApoE基因多态性为冠心病的危险因素，比值比OR分别为5.04，3.64，2.37，3.51，3.33。ApoE基因多态性与高血压史、高血脂史、Cpn感染、CMV感染间交互作用指数分别为1、73，1.55，1.28，1.20，归因交互百分比分别为40.64％，33.25％，19.01％和15.15％。结论 高血压史、高血脂史、Cpn感染、CMV感染和ApoE基因多态性可能是冠心病的主要危险因素，且ApoE基因多态性与其它危险因素在致冠心病的关系中存在正交互作用。     

阿尔茨海默病与EB病毒及ApoE基因多态性关系

目的 探讨EB病毒感染和ApoE基因多态性对阿尔茨海默病发病的影响.方法 用间接ELISA法测定18例阿尔茨海默病(AD)病人和20例正常对照者血浆中抗EB病毒特异性IgG、IgM类抗体;PCR法检测样本有核细胞和血浆中EB病毒DNA;通过直接测序法检测载脂蛋白E基因的基因型并分析其单核苷酸多态性.结果 AD病人血浆中抗EB病毒核心抗原(VCA)特异性IgG类抗体阳性率较正常对照明显升高(P＜0.05).AD组患者有核细胞和血浆中EBV DNA检出率高(分别为66.7%和50%),含ε4等位基因的基因型频率在AD和对照组之间差异有统计学意义(P＜0.05);阿尔茨海默病的发病与EBV感染和携带外周载脂蛋白Eε4(ApoEε4)呈明显相关(P=0.017).结论 EB病毒潜伏感染和携带ApoEε4对AD发病起到一定作用,2种因素同时存在可能是AD发病的危险因素.     

Effect of cigarette smoking and coffee consumption on apolipoprotein B levels

Apolipoprotein B levels were studied in relation to cigarette smoking, coffee and alcohol consumption, physical activity, age and body mass index in 253 men aged 21–61 years. The mean apolipoprotein B level was 7.3 ± 3.2 mg/dl and was higher for smokers compared with non-smokers. Considering the smokers of over 20 cigarettes/day and the non-smokers, this difference reached 12.6 ± 4.3 mg/dl. A significant increase of 7.2 ± 3.5 mg/dl in apolipoprotein B levels was observed in the subjects who drank over 3 cups of coffee/day compared with the remaining subjects, but the increase was only 4.3 ± 3.7 mg/dl when we made a correction for cigarette consumption. Furthermore, for cigarette smoking and coffee consumption, there is apparently an interactive effect with BMI and/or age (vs apolipoprotein B levels). However, with a stepwise selection among explicative variables [age, BMI, smoking (yes/no) and coffee consumption ( 3, > 3 cups/day)] and all their interactions of first order, only the interaction between BMI and smoking (BMI^*smoking: b± ES (b) = 0.3029±0.0303), and age and BMI (age^*BMI), are significantly and positively related to serum levels of apolipoprotein B. Thus cigarette smoking, interacting with high BMI, appear related to higher apolipoprotein B levels.Corresponding author.     

Apolipoprotein E polymorphism and plasma lipid, lipoprotein, and apolipoprotein levels in Italian children.

We have investigated the effect of apolipoprotein (apo) E polymorphism on serum lipid, lipoprotein, and apolipoprotein levels in a sample of 195 children, aged 8-11 years, from Sezze, Central Italy. The relative frequencies of e2, e3, and e4 alleles were 0.062, 0.867, and 0.072, respectively. Variation at the apo E gene locus explained 5.1% of the sample variance in serum total cholesterol levels, 7.6% in low-density lipoprotein (LDL) cholesterol levels, 7.3% in apo B levels, and 14.1% in high-density lipoprotein-apo E (HDL-E) levels. The effect of the e2 allele was to lower levels of total cholesterol, LDL-cholesterol, and apo B and to raise levels of HDL-E, while the effect of the e4 allele was the opposite. Variation at the apo E gene locus was not associated with differences in serum triglyceride, HDL-cholesterol, or apo AI levels. The effects of common apo E polymorphisms and genetic variation associated with the PvuII RFLP of the apo B gene on serum apo B levels were additive, explaining 11.3% of the phenotypic variance in this sample. When the effect of apo E polymorphism on serum lipid traits was estimated in boys and girls separately, variation at the apo E gene locus explained 10.4, 13.3, 13.3, and 13.5% of the phenotypic variance in serum total cholesterol, LDL-cholesterol, apo B, and HDL-E levels, respectively, in boys, while in girls only the effect on HDL-E levels (19.3%) reached statistical significance. This study has demonstrated that genetic variations at the apo E locus contribute to the determination of serum lipid, lipoprotein, and apolipoprotein levels in youths and that the effects are gender specific.     

高分辨熔解曲线检测潮汕汉族人群的载脂蛋白E基因多态性

目的研究载脂蛋白E(apo E)基因单核苷酸多态性各等位基因及基因型在潮汕汉族人群中的分布频率,比较其在不同种族间分布的差异。方法采用高分辨熔解曲线分型技术检测100例潮汕地区汉族人群的Apo E基因rs429358和rs7412多态性。PCR-测序法作为金标准进行比对。结果在潮汕地区汉族人群中存在Apo E基因rs429358和rs7412多态性。潮汕人的Apo E基因型分布以E3/E3最常见,其次为E4/E3。与非洲及欧洲人群比较,Apo E基因多态性的分布频率均存在显著性差异(P<0.05);而与中国汉人比较差异无显著性(P>0.05)。结论采用高分辨熔解曲线法进行Apo E基因多态性检测,其操作简便省时,不易交叉污染;获得的各种基因类型特征性强,适用于临床陕速诊断分型和遗传学人群研究。Apo E的3种常见等位基因频率分布存在地域差异。     

载脂蛋白E基因多态性与2型糖尿病患者轻度认知功能障碍的相关性研究

目的探讨载脂蛋白E（ApoE）基因多态性与2型糖尿病（T2DM）患者轻度认知功能障碍（MCI）的相关性及T2DM合并MCI的相关危险因素。方法选择T2DM合并MCI患者40例,T2DM非MCI患者80例,应用聚合酶链式反应-限制性片段长度多态性（PCR—RFLP）方法检测ApoE的基因多态性,依据病程、血糖、血脂、体重指数等临床资料,进行非条件logistie回归分析T2DM合并MCI的独立危险因素。结果ApoE￡。等位基因的频率在T2DMMCI组高于非MCI组（25．0％vs10．0％）,差异有统计学意义（P〈0．01）。T2DM合并MCI组与非MCI组差异有统计学意义的指标：年龄、病程、餐后2h血糖、糖化血红蛋白、体重指数、糖尿病家族史、高血压、糖尿病视网膜病变、糖尿病周围神经病变、ApoE基因,其中独立危险因素有糖尿病视网膜病变（OR=3．452,P〈0．05）、周围神经病变（OR=3．252,P〈0．05）、ApoE基因（OR=2．441,P〈0．01）、糖化血红蛋白（OR=1．372,P〈0．05）、餐后2h血糖（OR=1．194,P〈0．05）、年龄（OR=1．194,P〈0．01）、病程（OR=1．142,P〈0．05）。结论ApoE8。等位基因与T2DM合并MCI明显相关,糖尿病患者的年龄、病程、血糖控制和微血管并发症均与认知功能明显相关。     

长寿与非长寿者子代血脂水平及与apoE基因多态性的关系

目的　探讨遗传基因与血脂谱水平差异的关系。方法　对比分析 7个维吾尔族长寿家系的 86名子孙与 9个维吾尔族非长寿家系的 6 2名子孙的血脂谱水平和apoE等位基因频率分布差异 ,以及apoE基因多态性与血脂谱水平的关系。结果　调整年龄、工作性质后 ,长寿家系子孙不论男女 ,血脂谱中与动脉硬化呈正相关的指标均低于非长寿家系子孙 ,而与动脉硬化呈负相关的指标均高于非长寿家系子孙。其中男性甘油三酯 (1 49± 0 14)mmol/L、apoB(0 83± 0 0 4)g/L均显著低于非长寿家系子孙的 (2 11± 0 17)mmol/L和 (1 0 2± 0 0 5 )g/L ,高密度脂蛋白 胆固醇 /低密度脂蛋白 胆固醇 (0 74± 0 0 4)显著高于非长寿家系子孙 (0 5 9± 0 0 5 ) ,女性apoA/apoB(1 74± 0 0 8)显著高于非长寿家系子孙 (1 42± 0 0 9)。长寿家系子孙中等位基因ε4的相对频率 (5 8)显著低于非长寿家系子孙(16 1)。进一步分析发现 ,ε4等位基因携带者血清中总胆固醇、低密度脂蛋白 胆固醇、apoB水平显著高于其他等位基因携带者。结论　长寿家系子孙血脂谱综合指标优于非长寿家系子孙 ,apoE等位基因多态性可以部分地解释形成这种差异的原因     

载脂蛋白E基因多态性对肥胖儿童体质指数与血脂的影响

目的 研究载脂蛋白E（ApoE)基因多态性对单纯肥胖儿童体质指数（BMI）与血脂的影响。方法 检测324名8～12岁单纯肥胖儿童的血脂,测量体重和身高,计算BMI,同时使用多聚酶链反应检测他们的ApoE基因型。结果 E3/3是最常见的基因型,ApoE基因型分布为:E3/3 198人（61.1%),E3/4 36人（11.1%),E2/3 54人(16.7%）,E4/4 36人（11.1%）,未检测到E2/2和E2/4两种基因型。在ApoE 3组中,BMI与所有血脂指标呈明显相关。除低密度脂蛋白-胆固醇（LDL-C）、TC、载脂蛋白B(ApoB）外,其他血脂指标与BMI的相关性在其他ApoE组中则不尽相同。在ApoE2组中,BMI与TG呈明显相关,与高密度脂蛋白-胆固醇（HDL-C）、ApoA I无明显相关;在ApoE 4组中,BMI与HDL-C,ApoA I明显相关,而与TG无明显相关。结论 ApoE基因多态性可能对单纯肥胖儿童BMI与血脂的关系有一定影响。     

载脂蛋白A5基因多态性对代谢综合征及其心血管事件发生的影响

目的 探讨载脂蛋白A5(ApoA5)基因多态性对代谢综合征及其心血管事件发生的影响.方法 选择代谢综合征患者200例[其中未合并心血管事件患者100例(MS-1组),合并心血管事件100例(MS-2组)]和健康人100例(对照组).用ELISA法检测各组的载脂蛋白A5血清浓度,采用PCR-RFLP法测定三组的ApoA5-1131T＞C基因多态性.结果 MS-1组ApoA5血清浓度明显低于对照组[(96.68±18.09) ng/ml vs(128.32 ±23.78) ng/ml,t=10.59,P＜0.01];MS-2组ApoA5血清浓度亦低于MS-1组[(87.67±17.09) ng/ml vs(96.68±18.09) ng/ml,t=3.62,P＜0.01];而且MS-2组、MS-1组的ApoA5-1131C基因型频率明显高于对照组(39.4％＞30％＞16.5％,P＜0.05).结论 代谢综合征及其心血管事件患者的ApoA5血清浓度明显降低,ApoA5-1131C与代谢综合征及其心血管事件相关.     

The effect of dietary fat on LDL size is influenced by apolipoprotein E genotype in healthy subjects

LDL particle size is dependent on both genetic factors and environmental factors such as dietary fat composition. The apolipoprotein E (apoE) genotype is a major genetic determinant of LDL size. Thus, the aim of this work was to study whether the apoE genotype interacts with the quantity and quality of dietary fat, modifying LDL size in young healthy subjects. Healthy subjects (n = 84; 66 apoE 3/3, 8 apoE 4/3, 10 apoE 3/2) were subjected to 3 dietary periods, each lasting 4 wk. The first was an SFA-enriched diet (38% fat, 20% SFA), which was followed by a carbohydrate (CHO)-rich diet (30% fat, < 10% SFA, 55% carbohydrate) or a monounsaturated fatty acid (MUFA) olive oil-rich diet (38% fat, 22% MUFA) following a randomized crossover design. At the end of each diet period, LDL particle size and plasma levels of total cholesterol, LDL cholesterol (LDL-C), HDL-C, apoB, apoA-I, and triacylglycerols were determined. LDL particle size was significantly higher (P < 0.04) in subjects with the apoE 4/3 genotype compared with those with apoE 3/3 and apoE 3/2 in the basal state. LDL size was smaller (P < 0.02) after the CHO diet than after the MUFA or SFA diets. After the CHO diet, a significant increase in LDL particle size (P < 0.035) was noted with respect to the MUFA diet in apoE 4/3 subjects, whereas a significant decrease was observed in the apoE 3/3 individuals (P < 0.043). In conclusion, a Mediterranean diet, high in MUFA-fat increases LDL particle size compared with a CHO diet, and this effect is dependent of apoE genotypes.     

北京市城区学龄儿童载脂蛋白E多态性与血脂谱水平的关系

目的 了解载脂蛋白E（ApoE)基因多态性与儿童血脂谱水平的关系。方法 采用聚合酶链反应－限制性内切酶图谱分析法,对307名7－11岁在校儿童进行血脂谱水平测定及ApoE基因多态性检测.结果 307名儿童最常见基因型E3／3检出率为54．7％,其他基因型依次为E4／3（23．8％）、E4／4（9．1％）、E3／2（8．1％）、E4／2（3．9％）、E2／2（0．3％）,不同性别基因型构成的差异无显性;常见等位基因E3频率为70．7％,E4、E2分别为23．0％和6．4％,其中E4频率明显高于国内其他报道,E2频率接近于国内报道;男童E4／3、E3／3基因型总胆固醇（TC,4．19、4．29、3．41mmol/L)、低密度脂蛋白－胆固醇（LDL－C）、载脂蛋白AI（ApoA I)、载脂蛋白B（ApoB)水平高于E3／2基因型,E4／2基因型TC（4．28和3．42mmol/L)、ApoA I水平高于E3／2基因型,女童不同基因型血脂谱水平的差异无显性;高胆固醇组与正常组儿童ApoE-Hha I位点基因型分布比较差异无显性;ApoE2可使TC水平降低0．377mmol/L,LDL-C水平降低0．329mmol/L。结论 ApoE基因多态性与男童血清胆固醇水平相关,E2等位基因携带TC、LDL－C、ApoB水平最低。