12周高强度间歇训练对不同基因型载脂蛋白E血脂异常人群的调脂作用

目的:观察12周高强度间歇训练(HIIT)对不同载脂蛋白E(ApoE)基因型血脂异常人群的血脂调节作用。方法:通过测试空腹血脂指标,筛选出88例血脂异常患者作为受试对象,采集受试对象口腔粘膜进行载脂蛋白E基因型检测,测定12周高强度间歇训练干预前后的血脂水平。结果:88例血脂异常者中共检测出5种基因型,其分布为ApoE3/3＞ApoE3/4 ＞ApoE2/3＞ApoE2/2＞ApoE2/4,等位基因ε3＞ε2=ε4。运动干预前,血脂异常人群中ε4等位基因组的总胆固醇水平显著高于ε2和ε3基因组(P＜0.01),低密度脂蛋白胆固醇水平显著高于ε2基因组(P＜0.05),其余指标在各组间无显著性差异(P＞0.05)。12周的高强度间歇训练显著降低ε3基因组血清总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平,升高高密度脂蛋白胆固醇水平。ε4基因组在运动干预后血清总胆固醇和低密度脂蛋白胆固醇降低,甘油三酯和高密度脂蛋白胆固醇无显著性改变。ε2基因组在运动干预后血清脂质无明显改善。结论:血脂异常人群载脂蛋白E基因多态性影响运动的调脂效果,12周高强度间歇训练可以作为ε3和ε4等位基因携带者调节血脂的运动干预方式。     

中国北方人群TCF7L2 基因多态性与血脂谱的相关性

目的:研究中国北方人群TCF7L2基因rs11196218和rs290487多态性的分布特点及其与血脂谱的相关性。方法:对1255例中国北方人群TCF7L2基因进行单核苷酸多态性检测,同时检测其血脂水平,分析血脂水平与上述基因的相关性。结果:在中国北方人群中TCF7L2基因rs11196218位点AA,AG和GG基因型频率分别为6.61%,39.68%和53.71%,等位基因A、G频率分别为26.45%和73.55%;而rs290487位点TT,CT和CC基因型频率分别为37.45%,45.98%和16.57%,等位基因T,C频率分别为60.44%和39.56%。rs11196218A/G与血清低密度脂蛋白、总胆固醇水平具有相关性(P≤0.05),而rs290487C/T与血脂水平无相关性(P0.05)。结论:在中国北方人群中存在TCF7L2基因rs11196218A/G和rs290487C/T单核苷酸多态性,且其变异频率大,rs11196218A/G与血脂异常相关。     

彝族、藏族与哈尼族血清胆硷酯酶的遗传多态性

按照Kalow等的方法对中国3个人群的血清胆硷酯酶(简称ChE)的遗传多态性进行了研究。3个人群是四川省布拖县彝族(197人)、西藏自治区拉萨市藏族(100人)及云南省元江县哈尼族(170人)。根据每一个体的地布卡因值和氟化钠值,按Motulsky的分型标准进行分型。结果表明,在彝族中有3人属一般型+抗氟化物型(UF);在藏族中有2名UF;在哈尼族中也有3名UF,未发现不典型型(即抗地布卡因型的纯合子与杂合子),也未发现抗氟化物型的纯合子。因此,E_1~f基因频率在彝族、藏族与哈尼族中分别为0.0076、0.0100及0.0088。正常的常见等位基因E_1~(?)的频率分别为0.9924、0.9900及0.9912。这3个人群ChE表型分布均符合Hardy-Weinberg平衡法则。他们的基因频率与蒙古人种其他人群是一致的。     

ApoE基因多态性与早发冠心病关系的研究

目的:研究载脂蛋白E(ApoE)基因多态性与早发冠心病CHD)的关系。方法:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)基因分析方法,测定92例早发CHD、237例迟发CHD患者和220名对照者的ApoE基因型;血脂水平按常规方法测定。结果:发现的5种ApoE基因型,分别为E3/3、E2/2、E3/2、E4/3及E4/2。早发CHD组和迟发CHD组ApoE 4/3基因型和ε4等位基因频率均高于对照组(P＜0．01);进一步对两组CHD患者的ApoE多态性进行分析,发现早发组ε4等位基因频率较迟发组高(P＜0．05)。ApoE各等位基因型之间,TC和LDL-C水平之间存在统计学差异(P＜0．05)。结论:ApoE基因多态性与早发CHD的发生发展有关。     

玉米酯酶同工酶和过氧化物酶同工酶的分子量研究

本试验利用聚丙烯酰胺凝胶梯度电泳分步染色法直接对玉米苗期酯酶同工酶和过氧化物酶同工酶各酶带的分子量进行了比较测定。酯酶同工酶 E_1、E_2、E_3~F、E_3~S、a、b、c 各酶带的分子量分别为<20000,35200、33000、38500、29900、28500、34000道尔顿过氧化物酶同工酶 PX_4~F和 PX_4~S酶带的分子量分别为131000和149000道尔顿。根据酶带在均匀胶和梯度胶中的位置变化对各酶带的生化性质作了初步分析,发现 E_3~F和 E_3~S、PX_4~F 和 PX_4~S 在迁移率上的差异主要是分子量的差异。本文为同工酶的分子量测定提供了一个简便的方法。     

广西普通野生稻(Oryza rufipogon Griff)表型性状和SSR多样性研究

以中国普通野生稻初级核心种质中广西普通野生稻部分中的 2 2 3份野生稻为材料 ,以平均分布于水稻 12条染色体上的 34对SSR引物和中国稻种资源目录中的表型性状分析广西普通野生稻SSR位点的等位变异、多样性的地理分布及不同生长习性间的多样性分布等。结果表明 ,每对引物检测到的多态性片段 7～ 4 8条 ,平均为 2 4 .91条 ,普通野生稻的等位变异数明显大于地方稻种 ,在所分析的SSR位点中杂合位点比例变化在 1.35 %～ 81.31%之间 ,平均为 32 .0 1% ,与自花授粉的栽培稻相比具有较高的杂合率 ;北纬 2 2°～ 2 3°和 2 3°～ 2 4°范围内的两个区域内(一个包括隆安、扶绥和邕宁三县 ,另一个包括象州、来宾、武宣、玉林和贵港五个县 )所包含的普通野生稻数量多 ,遗传多样性大 ,在DNA水平上是广西普通野生稻的遗传多样性中心 ,而表型性状多样性中心是在北纬 2 1°～ 2 2°和2 2°～ 2 3°,其多样性分布与DNA水平不完全一致。在 4种生长习性间 ,DNA水平上的遗传多样性大小依次为匍匐型 ,倾斜型 ,半直立型和直立型 ,表型水平的多样性与DNA水平的多样性基本一致。     

载脂蛋白E基因多态性与持续性植物状态的关系及其意义

研究载脂蛋白E(ApoE)基因多态性与持续性植物状态 (PVS)之间的关系 ,探讨PVS发生的遗传背景及其对血脂水平的影响。以 6 2名PVS患者为研究对象 ,5 5名正常人为对照 ,采用聚合酶链反应和限制性片段长度多态性(PCR RFLP)方法 ,分析了载脂蛋白E基因多态性 :血脂水平按常规酶法进行测定并进行统计学处理。ApoE基因多态分析表明 ,在PVS患者和正常人中观察到 5种ApoE基因型 ,分别为E3/ 3、E3/ 4、E2 / 2、E2 / 3及E4 / 2。PVS患者组ApoE3/ 4基因型频率高于对照组 (χ2 =14 .2 36 ,P <0 .0 0 1) ;而E3/ 3基因型频率较对照组显著降低 (χ2 =5 .348,P <0 .0 5 )。PVS患者的ε4等位基因频率显著高于对照组 (χ2 =10 .5 33,P <0 .0 0 1) ;而ε3等位基因频率显著低于对照组 (χ2 =7.0 2 2 ,P <0 .0 1)。两组ApoE基因型E2 / 2 ,E2 / 4 ,E2 / 3,E3/ 4的低密度脂蛋白胆固醇 (LDL C)水平之间存在统计学差异 (P <0 .0 5 ,P <0 .0 5 ,P <0 .0 5 ,P <0 .0 1)。ApoE基因多态性与PVS有关联 ,并影响患者的血脂水平。ApoE基因多态性可能与PVS的发生和预后有关     

正常月经周期妇女卵泡液中激素水平的变化

本文测定了24例正常月经妇女在不同时相、不同大小卵泡的卵泡液中雌二醇(E_2)、孕酮(P_0)、雄烯二酮(A)、睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)和催乳素(PRL)的含量,并分析其与外周血中相应激素浓度的关系。测定结果显示:小卵泡的卵泡液中E_2、Po,FSH,LH水平低于大卵泡中水平,而A和T水平则相反。排卵前大卵泡中E_2(9815nmol/L),P_0(3316nmol/L),FSH(1.34IU/L)和LH(3.9lIU/L)达最高值。A(280nmol/L)和T(137nmol/L)却较小卵泡中水平低(相应为692nmol/L和176nmol/L)。PRL水平在大小卵泡中无显著性差异。卵泡液中甾体激素水平高于外周血7—20.000倍,FSH、LH水平为外周血的10—80％,PRL水平为60％—3倍。     

团头鲂血清中雌二醇含量测定方法的改进和周年变化规律的研究

采用加热处理的方法代替了用有机溶剂进行血清样品抽提的繁琐步骤,为鱼类血清雌二醇(E_2)放射免疫测定摸索了一种简单易行的方法。对团头鲂(Megalobrama arablycephala)雌鱼血清中E_2含量的周年变化进行了测定。1—4月血清E_2含量逐渐上升,1月份为全年最低值(0.61±0.28ng/ml),4月份达到最高值(5.63±0.85ng/ml),之后,血清E_2含量明显下降。10—12月E_2水平维持在1.62±0.20ng/ml左右,形成一个持续三个月的小峰。卵巢成熟系数与血清E_2含量的变化,两者之间呈正相关,r=0.6089。并呈现出E_2含量的升高先于成熟系数的增长,E_2含量在产卵季节前一个月达到高峰值。表明血清E_2含量的变化与性腺在早春的发育生长密切相关,而与性腺晚期的发育成熟关系不大。10—12月的一个小峰与产后性腺的复发,即性腺再度进入卵黄发生期有关。     

甲醚抗孕丸对妇女雌激素排泄的影响

本工作用气相层析方法测定了7名正常妇女和11名服甲醚抗孕丸妇女尿中 E_3、E_2、E_0和 P_2含量的周期变化,观察到11名服药妇女中有6名排卵受到抑制(P_2<1mg/天),其余5名有排卵(P_2>2.5mg/天)。服药后无排卵的妇女尿中雌激素周期变化的特点是雌激素在后半周期有较大幅度的升高。部分服药后有排卵的妇女尿中三种雌激素的比例出现异常,E_2或 E_0含量高于 E_3,反映了体内 E_2的正常代谢受到了干扰。文中对服药后引起的激素周期变化与抗生育的关系作了简略的分析和讨论。     

High degree of genetic polymorphism in apolipoprotein(a) associated with plasma lipoprotein(a) levels in Japanese and Chinese populations

We have developed a sensitve, high-resolution method for the analysis of the apolipoprotein(a) [apo(a)] isoforms using sodium dodecyl sulfate (SDS)-agarose/ gradient polyacrylamide gel electrophoresis. In an analysis of the genetic polymorphism of apo(a) isoforms and their relationship with plasma lipoprotein(a) [Lp(a)] levels in Japanese and Chinese, this method identified 25 different apo(a) isoforms and detected one or two apo(a) isoforms in more than 99.5% of the individuals tested. The apparent molecular weights of the apo(a) isoforms ranged from 370 kDa to 950 kDa, and 22 of the 25 different apo(a) isoforns had a higher molecular weight than of apo B-100. Studies on Japanese families confirmed the autosomal codominant segregation of apo(a) isoforms and the existence of a null allele at the apo(a) locus. The observed frequency distribution of apo(a) isoform phenotypes fit the expectations of the Hardy-Weinberg equilibrium in both the Japanese and Chinese populations. Our data indicate the existence of at least 26 alleles, including a null allele, at the apo(a) locus. The frequency distribution patterns of the apo(a) isoform alleles in Japanese and Chinese were similar to each other and also similar to that of apo(a) gene sizes reported in Caucasian American individuals. The average heterozygosity at the apo(a) locus was 92% in Japanese and 93% in Chinese. A highly significant inverse correlation was observed between plasma Lp(a) levels and the size of apo(a) isoforms in both the Japanese (r=-0.677, P=0.0001) and the Chinese (r=-0.703, P=0.0001). A highly skewed distribution of Lp(a) concentrations towards lower levels in the Japanese population may be explained by high frequencies of alleles encoding large apo(a) isoforms and the null allele.     

Genetic control of human apolipoprotein E polymorphism: Comparison of one-and two-dimensional techniques of isoprotein analysis

Summary Genetic polymorphism of human apolipoprotein E (apo E) has previously been demonstrated by one-dimensional isoelectric focusing (Utermann et al. 1977b) and by two-dimensional electrophoresis of apolipoproteins (Zannis et al. 1981), but the relationship between the results obtained by these methods remained unclear. We therefore performed comparative phenotyping by one-dimensional and two-dimensional electrophoresis. Apoproteins from very low-density lipoproteins (apo VLDL) prepared by ultracentrifugation or from an apo Erich lipoprotein fraction prepared by heparin/Mg⁺⁺ precipitation, were used as a source of apo E. Six common phenotypes designated apo E-4/4, apo E-N/N, apo E-D/D, apo E-4/N, apo E-4/D, and apo E-N/D were differentiated irrespective of the technique used or the source of apolipoproteins, but the two-dimensional electrophoresis of apo VLDL and apo VLDL which had been treated with neuraminidase was the key for the correct genetic interpretation of those phenotypes exhibiting the E4 isoform of the protein. Each phenotype is characterized by the presence of either one or two of three major isoforms E2, E3, and E4 and by the presence of several minor sialylated forms of these proteins (apo E_s) that have higher apparent molecular weights. The unsialylated major isoform apo E2 does not only differ in charge but also has a higher apparent mol.wt. (about 34,500) than the major isoforms apo E3 and apo E4 (mol. wt. about 33,000). Family studies including 90 matings with a total of 203 offspring confirmed the genetic one locus model of Zannis et al. (1981). Apo E phenotypes are controlled by three autosomal codominant alleles apo E^d, apo Eⁿ, and apo E⁴ that specify for the E2, E3, and E4 isoforms respectively. Phenotypes apo E-D/D,-N/N, and-4/4 represent homozygotes and phenotypes apo E-4/N,-4/D, and-N/D heterozygotes for these alleles.The frequencies of apo E alleles in 1031 blood donors were apo E⁴=0.150, apo Eⁿ=0.773, and apo E^d=0.077. Homozygosity for the allele apo E^d is associated with hyperlipoproteinemia type III. Hence a large number of the population (about 1%) are at risk for this specific lipoprotein disorder that is associated with premature atherosclerosis and xanthomatosis.     

Apolipoprotein E genotypes and metabolic risk factors for coronary heart disease in middle-aged women

Apo E genotypes and plasma metabolic risk factors (total cholesterol, triglycerides, HDL and LDL cholesterol, total/HDL cholesterol ratio, lipoprotein Lp (a), apolipoprotein A-I, A-II, apo B, and apo E) were determined in 134 healthy middle-aged (X +/- SD 49.62 +/- 4.83) women. The aim of this study was to investigate metabolic risk markers according to various apo E genotypes, and to evaluate a possible risk for coronary heart disease. The results revealed that the frequencies of apo E3/3 are the most frequent (46%), followed by E4/4 (2%), E3/4 (14%), E2/3 (14%), and E2/4 (2%) in the middle-aged women. Higher mean triglycerides, LDL-C and apo B levels were found with apo E3/4, and lower mean levels of HDL-C i.e. apo A-I than in other analyzed genotypes. Greater mean of total/HDL ratio and lower levels of apo A-II were seen with E2/4. Serum lipoprotein Lp (a) concentration was higher in women with genotypes E3/3. Apo E concentration was the lowest with genotypes E4/4, i.e. the highest with E2/3. Serum total cholesterol tended to be higher in women with genotypes E4/4. Genotype E3/4 is connected with the highest concentrations of (X +/- SD) triglycerides (1.74 +/- 0.78), LDL (4.28 +/- 1.88), apo B (1.03 +/- 0.32) and with the lowest concentrations of HDL cholesterol (1.11 +/- 0.21) in the relation to the other analyzed genotypes. This group of women could possibly represent high risk women for CHD. Genotype E3/3 is associated with the highest concentration of independent genetic risk marker for CHD, lipoprotein Lp (a) (0.19 +/- 0.27). The genotype E4/4 has the highest concentration of total cholesterol (5.93 +/- 1.01), and has to be taken in account for risk evaluation in women. High level of apo E (0.11 +/- 0.05) and low level of apo A-I (1.80 +/- 0.44) were associated with E2/3 genotypes. The significance of E3/4 with the high total/HDL ratio (5.52 +/- 2.21) and low apo A-II (0.53 +/- 0.09) is important indicator, because total/HDL cholesterol ratio represents independent Established Risk Factor (ERF) for CHD. Apolipoprotein E genotypes as genetic markers and investigation of serum metabolic risk markers appear to be important in view for further evaluation of high risk women for CHD in our population.     

Apolipoprotein E phenotypes in patients with myocardial infarction

Summary The frequencies of genetic apo E isoforms E2, E3 and E4 were determined in 523 patients with myocardial infarction and compared to those in a control group (1031 blood donors). A significant difference in the frequency of apo E4 was noted between patients and controls (0.05> P>0.025). No differences in the frequencies of isoforms E3 and E2 were observed. In particular, there was no significant difference between the two groups in the frequency of apo E2 homozygosity. a condition that is associated with type III hyperlipoproteinemia. However, all E2 homozygote survivors of myocardial infarction had hyperlipoproteinemia type III (cholesterol 269±29 mg/dl; triglyceride 419±150 mg/dl; age 54±14 years; N=5). On the contrary, E2 homozygote controls (all apo E-2/2 blood donors and their apo E-2/2 relatives who were from the same age range as the patients) had primary dysbetalipoproteinemia but normal or subnormal plasma cholesterol concentrations (cholesterol 184±28 mg/dl; triglyceride 151±52 mg/dl; age 56±13 years; N=11). This indicates that E2 homozygotes with hyperlipoproteinemia type III who occur rarely in the population but comprise about 1% of myocardial infarction patients have a markedly increase risk for coronary atherosclerosis, whereas the risk for E2 homozygotes with normal or subnormal plasma cholesterol (=primary dysbetalipoproteinemia) may be considerably lower than for the general population. The data illustrate the complex relationship between apo E genes, lipid levels, and risk for atherosclerosis.     

Activation of phosphatidylcholine-sterol acyltransferase by human apolipoprotein E isoforms

The reaction catalysed by phosphatidylcholine-sterol acyltransferase (EC 2.3.1.43) is believed to be the major source of cholesteryl ester in human plasma; the enzyme requires a protein activator. Several human apolipoproteins were found to exhibit an activator function, the major one being apolipoprotein A-I. Human apolipoprotein E exists in the population mainly in three different genetic isoforms; apolipoprotein E-2, E-3 and E-4. These isopeptides were isolated from subjects homozygous for one of the isoforms, incorporated into phospholipid/cholesterol/[14C]cholesterol complexes by the cholate dialysis procedure and used to measure capacity to activate phosphatidylcholine-sterol acyltransferase in comparison to apolipoprotein A-I lipid substrate particles prepared by the same procedure. Acyltransferase activity was measured by the formation of [14C]cholesteryl ester from [14C]cholesterol using purified enzyme. With egg yolk phosphatidylcholine as acyl donor, apo E was 15-19% as efficient as apolipoprotein A-I for activation of the acyltransferase. Apo-E-stimulated cholesteryl ester formation by the enzyme was enhanced when 1-oleoyl-2-palmitoyl-glycerophosphocholine was used as a substrate phospholipid (45% of apo A-I/phosphatidylcholine control) and most pronounced with dimyristoylglycerophosphocholine (75% of apo A-I/phosphatidylcholine control). No significant difference in activation was found between apo E isoforms. It is concluded that apolipoprotein E activates phosphatidylcholine-sterol acyltransferase in vitro and that apolipoprotein E isoforms are similarly effective.     

Association of methylenetetrahydrofolate (MTHFR) and apolipoprotein E (apo E) genotypes with homocysteine, vitamin and lipid levels in carotid stenosis

The aim of the study was to investigate the association between methylenetetrahydrofolate (MTHFR) genotypes and levels of homocysteine (Hcy), folate, vitamin B12 and lipids as well as the association between apolipoprotein E (apo E) genotypes and levels of lipids in a Croatian healthy control group and a group of patients with > 70% carotid stenosis (CS). The study included 98 Croats, 38 patients with > 70% carotid stenosis and 60 age- and sex-matched controls. The MTHFR and apo E genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), Hcy by enzyme immunoassay, vitamins by immunochemiluminiscence, and lipids by spectrophotometric method. There was no difference between control subjects and CS patients in the distribution of C677T MTHFR genotypes (p=0. 786) and alleles (p=0.904), however, differences in the frequencies of apo E genotypes (p=0.012) and alleles (p=0.029) were statistically significant. The odds ratio for apo E 3/4 genotype was 3.93 (95% CI 1.23-12.61). Hyperhomocysteinemia (> or =15 micromol/L) was found in 11% of CS patients and 5% of control subjects. Total cholesterol, triglycerides, vitamin B12 and folate were statistically different in "all MTHFR genotypes" (p<0.001, p<0.01, p=0.044 and p=0.036, respectively), and in TC/TT (p<0.001, p=0.003, p=0.030 and p=0.032, respectively) groups. The levels of total cholesterol, LDL cholesterol and triglycerides in the apo E 3/3, and total cholesterol in the apo E 3/4 group yielded statistical difference. An association was found of apo E 3/4 genotype but not of MTHFR genotypes with the risk of CS. MTHFR and apo E affect blood lipid levels, which was statistically confirmed. An association was also recorded between hyperhomocysteinemia and patients with CS. Vitamin status in CS showed a statistically verified association with TC/TT MTHFR genotype. In the group of patients with TC/TT MTHFR genotype, lower vitamin B12 and higher folate values were recorded. The results of multiple logistic analysis showed that there was no statistical significance of Hcy levels (OR 2.403, p=0.334) or conventional vascular risk factors such as smoking habit (OR 0.505, p=0.149), age (OR 1.048, p=0.087) or sex (OR 2.037, p=0.112) in predicting CS.     

Characterization of apolipoprotein E genetic variations in Taiwanese: association with coronary heart disease and plasma lipid levels

Apolipoprotein E (apoE, protein; APOE, gene) is important in lipoprotein metabolism. Three isoforms, apoE2 (Cys112 Cys158), apoE3 (Cys112 Arg158), and apoE4 (Arg112 Arg158), are present in the general population. This report investigates the frequency distribution of apoE isoforms and the association of APOE genotypes with plasma lipid profile and coronary heart disease (CHD) in a population of Taiwan. ApoE isoforms were determined genetically by polymerase chain reaction and HhaI restriction enzyme digestion in control and coronary heart disease (CHD) patients. Plasma lipid and lipoprotein concentrations were also determined. The control group exhibited frequencies of 84.6% APOE3, 7.9% APOE4, 7.5% APOE2, 70.6% APOE3E3, 14.4% APOE3E4, 13.6% APOE2E3, and 1.4% APOE2E4. Comparable frequencies were observed in the CHD group. In both APOE2 carrier and APOE3E3 groups, the CHD patients expressed abnormal lipid profiles while the control group expressed normal lipid profiles. The APOE4 carriers, however, expressed abnormal lipid profiles in both normal control and CHD groups. Extremely high apoE levels in the hypertriglyceridemic group (TG > 400 mg/dL) seemed to be undesirable and were often observed in CHD patients.     

Human apolipoprotein E isoprotein subclasses are genetically determined.

In a recent communication, we showed that human very low density lipoprotein (VLDL) apolipoprotein E (Apo E) from different individuals appears upon two-dimensional gel electrophoretic analysis in either one of two complex patterns. These have been designated class alpha and class beta. Mixing of VLDL from different subjects revealed that not all alpha or beta apo E patterns were the same. In this manner, we identified three subclasses of class alpha (alpha II, alpha III, and alpha IV) and three subclasses of class beta (beta II, beta III, and beta IV). We report here the results of family studies that reveal that the subclasses (alpha II, alph III, and alpha IV and beta II, beta III, and beta IV) of apo E are determined at a single genetic locus with three common alleles, epsilon II, epsilon III, and epsilon IV. The class beta phenotypes (beta II, beta III, and beta IV) represent homozygosity for two identical apo E alleles (epsilon). In contrast, class alpha phenotypes (alpha II, alpha III, and alpha IV) represent heterozygosity for two different apo E alleles. The apo E subclasses and their corresponding genotypes are as follows: beta II = epsilon II/epsilon II; beta III = epsilon III; beta IV = epsilon IV/epsilon IV; alpha II = epsilon II/epsilon III; alpha III = epsilon III/epsilon IV; and alpha IV = epsilon II/epsilon IV. To estimate the frequencies of the apo E alleles in the general population, apo E subclasses were then investigated in 61 unrelated volunteers and the results were: beta II = 1 (2%), beta III = 30 (49%), alpha II = 9 (15%, alpha III = 13 (31%), and alpha IV = 2 (3%). Utilizing the frequencies of these phenotypes, the gene frequencies were calculated to be epsilon II = 11%, epsilon III = 72%, and epsilon IV = 17%. In addition, apo E subclasses were studied in a clinic for individuals with plasma lipid disorders and the apo E subclass beta IV was found to be associated with type III hyperlipoproteinemia. There was no association of any apo E subclass with type II, type IV, or type VI hyperlipoproteinemia or plasma HDL cholesterol levels. This study explains the genetic basis for the common variation in a human plasma protein, apo E. Since the apo E subclass beta IV is associated with type III hyperlipoproteinemia, a disease characterized by xanthomatosis and premature atherosclerosis, understanding the genetic basis of the apo E subclasses should provide insight into the genetics of type III hyperlipoproteinemia.     

The apolipoprotein E polymorphism: a comparison of allele frequencies and effects in nine populations.

Application of uniform methods for measuring the apolipoprotein (apo) E polymorphism and plasma cholesterol levels in nine populations (Tyrolean, Sudanese, Indian, Chinese, Japanese, Hungarian, Icelandic, Finnish, and Malay) revealed significant heterogeneity among them in apo E type frequencies and mean cholesterol levels. The major apo E types in all populations were E3/2 (frequency range from 7.0% in Indians to 16.9% in Malays), E3/3 (frequency range from 39.8% in Sudanese to 72.1% in Japanese), and E3/4 (frequency range from 11.3% in Japanese to 35.9% in Sudanese). Mean cholesterol levels ranged from 144.2 mg/dl in the Sudanese to 228.5 mg/dl in the Icelandics. Two-way analysis of variance of the effect of population and apo E type on cholesterol levels showed no significantly interaction effect, indicating that the effects of apo E type on cholesterol levels do not differ significantly among the populations. The overall average excess for the epsilon 2 allele was -14.12 mg/dl (range -31.63 to -8.82 mg/dl); for the epsilon 3 allele, 0.04 mg/dl (range -1.87 to 1.58 mg/dl; and for the epsilon 4 allele, 8.14 mg/dl (range -1.71 to 13.31 mg/dl). Despite the apparent heterogeneity in these values, especially for the epsilon 4 allele, comparison of the average excesses by a method of repeated sampling with random permutations revealed no significant difference in effects among populations. These data indicate that a given apo E allele acts in a relatively uniform manner in different populations despite differences in genetic background and environmental factors.     

Polymorphisms of apolipoproteins A-IV and E in a Turkish population living in Germany

Human apolipoproteins (apo) E and apo A-IV are polymorphic with significantly different allele frequencies among different ethnic groups. Whereas the variation at the apo E gene locus affects plasma cholesterol levels in all populations studied so far and is associated with longevity in Caucasians, the influence of the common apo A-IV polymorphism on plasma lipoproteins has not been unanimously accepted. We have therefore determined the common apo E and apo A-IV polymorphisms by isoelectric focusing, calculated the respective allele frequencies and studied their effects on plasma lipoproteins in a random sample of 240 nonrelated Turkish subjects (141 males, 99 females) living in Germany and originating from central and eastern Anatolia. When compared with the German population and other Caucasians in Europe a prominence of the apo ɛ3 allele frequency (0.885) was accompanied by a decrease in the frequencies of both the apo ɛ2 allele (0.048) and the apo ɛ4 allele (0.067). Thus, the Turkish population studied here clustered with populations mainly from southern Europe and Japan, which have low ɛ2 and ɛ4 allele frequencies. Also, the frequency of the A-IV-1 allele was higher (0.967) and that of the A-IV-2 allele lower (0.033) in the Turkish subjects studied than in other populations. At an average level of total cholesterol of 194.5 ± 45 mg/dl, no significant influence of the A-IV alleles on plasma lipoproteins was seen. However, apo E and apo B differed significantly between apo E phenotypes, with high levels of apo E and low levels of cholesterol and apo B in carriers of the ɛ2 allele, and vice versa for the ɛ4 allele. The average cholesterol excess for the ɛ2 allele was –7.95 mg/dl, for the ɛ3 allele, –1.34, and for the ɛ4 allele, +14.15 mg/dl. Thus, despite the unusual frequency distribution of the apo E alleles, their effects on plasma lipoproteins are within the range reported for other populations in Europe. Received: 10 April 1995 / Revised: 25 March 1996