汉族人载脂蛋白E基因多态性对血脂、载脂蛋白和脂蛋白(a)水平的影响

应用ＰＣＲ－ＲＦＬＰ技术研究我国汉族人群ａｐｏＥ基因型与等位基因频率分布特征，并分析ａｐｏＥ基因多态性对脂质代谢的影响。发现我国汉族人群ａｐｏＥε３等位基因频率（８３．２％）明显高于欧美人群，而ε４频率（７．５％）显著低于欧美人群。ε４与血清ＴＣ、ＬＤＬ－Ｃ和ａｐｏＢ水平增加呈显著正相关。ａｐｏＥ等位基因变异对血清ＴＧ、ＨＤＬ－Ｃ、ａｐｏＡＩ及Ｌｐ（ａ）水平无明显影响。研究提示，ａｐｏＥ基因多态性影响血清脂质和脂蛋白水平，我国汉族人群ａｐｏＥ基因多态性特征可能与中国人群冠心病患病率明显低于欧美人群相关。     

老年脑血管病患者脂蛋白（α）检测及其临床意义

用放免的方法测定了５０例脑血管病（ＣＶＤ）患者血清脂蛋白（α）［Ｌｐ（α）］浓度，对比分析了患者Ｌｐ（α）、甘油三脂（ＴＧ）、总胆固醇（ＴＣ）、高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）、低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）、脱脂蛋白Ａ－Ｉ（ａｐｏＡ－Ｉ）、ａｐｏＢ１００的浓度及变化，分析了Ｌｐ（α）浓度及ＴＧ、ＴＣ和胶脂蛋白的相关性。结果：ＣＶＤ患者血清Ｌｐ（α）浓度（０．２２４±０．０４ｇ／Ｌ），显著高于对     

高胆固醇血症大鼠LDL受体与apoA－1mRNA的水平变化及苯甲酸雌二醇对其影响

本文研究了实验性高胆固醇血症大鼠肝及小肠中低密度脂蛋白（ＬＤＬ）受体ｍＲＮＡ和载脂蛋白（ａｐｏ）Ａ－１ｍＲＮＡ的水平变化以及苯甲酸雌二醇（ＥＢ）对二者的影响。发现高脂（ＨＣ）组肝及小肠ＬＤＬ受体ｍＲＮＡ水平分别低于正常组５０％和６０％（Ｐ＜０．０５），小肠ａｐｏＡ－１ｍＲＮＡ水平低于正常组５８％（Ｐ＜０．０５），此时血清总胆固醇（ＴＣ）及ＬＤＬ胆固醇（ＬＤＬ－ｃ）均明显高于正常组（Ｐ＜０．０１），血清ａｐｏＡ－１低于正常组（Ｐ＜０．０５）。ＨＣ＋ＥＢ组血清ＴＣ及ＬＤＬ－ｃ明显低于ＨＣ组，而肝ＬＤＬ受体ｍＲＮＡ水平则显著高于ＨＣ组，为ＨＣ组的３．５倍（Ｐ＜０．００２）。结果提示：（１）高胆固醇负荷时细胞可通过转录水平下行调节ＬＤＬ受体；（２）小肠可能在ａｐｏＡ－１的代谢中起重要作用；（３）ＥＢ可能通过诱导肝ＬＤＬ受体基因表达而降血脂。     

中国人内源性高甘油三酯血症与载脂蛋白CⅢ基因Sst Ⅰ酶切位点多态性关联的研究

为观察中国人载脂蛋白ａｐｏＣⅢ基因变异的频率及其与内源性高甘油三酯血症（ＨＴＧ）的关联，应用多聚酶链反应（ＰＣＲ）对７４例正常人及６９例ＨＴＧ患者ａｐｏＣⅢ基因酶切位点的限制性片段长度多态性（ＲＦＬＰ）进行了研究。结果表明：ＨＴＧ患者和正常人均以Ｓ１等位基因（ＳｓｔⅠ－）为主。大多数为Ｓ１Ｓ１纯合子基因型；Ｓ２等位基因（ＳｓｔⅠ＋）少见，其频率显著高于白种人（０．２７９ｖｓ０．１２０，Ｐ＜０．００３）。ＨＴＧ组Ｓ２等位基因频率较正常对照组有增加趋势（０．３５３ｖｓ０．２７９，Ｐ＞０．０５）。ＨＴＧ组及对照组中具有Ｓ２Ｓ２基因型者与Ｓ１Ｓ１及Ｓ１Ｓ２基因型者比较，血清ａｐｏＣⅢ及ａｐｏＥ水平显著升高（Ｐ＜０．０２，Ｐ＜０．０５）及血清ＴＧ／ＨＤＬ－Ｃ比值显著升高（Ｐ＜０．０３）。推测ａｐｏＣⅢ基因ＳｓｔⅠ酶位点的ＲＦＬＰ与中国人ＨＴＧ可能有一定关联，ａｐｏＣⅢＳ２Ｓ２基因型对血清ａｐｏＣⅢ、ａｐｏＥ含量及ＴＧ／ＨＤＬ－Ｃ比值的升高有一定影响。     

载脂蛋白A－Ⅳ和实验性高脂血症时平滑肌细胞内的胆固醇转运

通过建立高胆固醇血症兔模型，观察载脂蛋白（ａｐｏ）Ａ－Ⅳ和ａｐｏＡ－Ⅳ／卵磷脂（ＰＣ）脂质体等对高胆固醇血症兔主动脉平滑肌细胞（ＳＭＣ）内胆固醇的清除及对血清卵磷脂胆固醇酰基转移酶（ＬＣＡＴ）的激活作用。结果显示，ａｐｏＡ－Ⅳ／ＰＣ脂质体清除ＳＭＣ内胆固醇及激活ＬＣＡＴ的能力与ａｐｏＡ－Ⅰ／ＰＣ脂质体、高密度脂蛋白（ＨＤＬ）相似。提示，ａｐｏＡ－Ⅳ与ａｐｏＡ－Ⅰ一样，在胆固醇逆向转运过程中起重要作用；ａｐｏＡ－Ⅳ与ＰＣ人工合成的脂质体有可能代替天然ＨＤＬ而发挥防治动脉粥样硬化的作用。     

男性冠心病患者性激素与脂蛋白（a）关系的初步探讨

目的：探讨男性冠心病患者性激素与血脂的关系。方法：分别用放射免疫法及ＥＬＩＳＡ法测定血清性激素及脂蛋白（ａ）［Ｌｐ（ａ）］水平，用酶法及透射比浊法测定血胆固醇及载脂蛋白浓度。结果：冠心病组血清睾酮（Ｔ）、高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）明显低于正常对照组（Ｐ＜００１），血清雌二醇与睾酮比率、Ｌｐ（ａ）明显高于正常对照组（Ｐ＜００１），而血清雌二醇（Ｅ２）、载脂蛋白及血浆总胆固醇（ＴＣ）两组间无显著差异（Ｐ＞００５）。冠心病组血清Ｔ水平与ＨＤＬ－Ｃ水平呈显著正相关（Ｐ＜００１），与Ｌｐ（ａ）水平呈显著负相关（Ｐ＜００５）；血清Ｅ２水平与Ｌｐ（ａ）水平无相关性。结论：睾酮下降为主的性激素失衡是男性冠心病的致病因子。     

高胆固醇血症大鼠LDL受体与apoA—1mRNA的水平变化及苯甲…

本文研究了实验性高胆固醇血症大鼠肝及小肠中低密度脂蛋白（ＬＤＬ）受体ｍＲＮＡ和载脂蛋白（ａｐｏ）Ａ－１ｍＲＮＡ的水平变化以及苯甲酸雌二醇（ＥＢ）对二者的影响。发现高脂（ＨＣ）组肝及小肠ＬＤＬ受体ｍＲＮＡ水平分别低于正常组５０％和６０％（Ｐ〈０．０５），小肠ａｐｏＡ－１ｍＲＮＡ水平低于正常组５８％（Ｐ〈０．０５），此时血清总胆固醇（ＴＣ）及ＬＤＬ胆固醇（ＬＤＬ－ｃ）均明显于正常组（Ｐ〈０．０１），血     

年轻冠心病患者子女血脂,脂蛋白,载脂蛋白的研究

本文对５２名父母于４５岁之前患冠心病的儿童和６３名父母无ＣＨＤ的儿童，进行ＴＣ，ＴＧ，ＨＤＬ－Ｃ，ａｐｏＡ－Ｉ，ａｐｏＢ－１００水平的对比研究。结果显示：父母较早发生ＣＨＤ的儿童，血清ＴＧ，ＴＣ，ａｐｏＢ－１００水平及ＴＣ／ＨＤＬ－Ｃ显著高于对照组；ＨＤＬ－Ｃ，ａｐｏＡ－Ｉ，ａｐｏＡ－Ｉ／ａｐｏＢ－１００水平显著低于对照组。     

载脂蛋白（a）的遗传学研究进展

脂蛋白（ａ）（Ｌｐ（ａ））是动脉粥样硬化的独立危险因子，它由载脂蛋白（ａ）（ａｐｏ（ａ））与ＬＤＬ中的ａｐｏＢ１００以二硫键连接而成。ａｐｏ（ａ）的结构与血浆纤溶酶原高度同源，其基因定位于６ｑ２６－２７，亦与纤溶酶原基因紧邻。ａｐｏ（ａ）受单一位点的至少１９个等位基因所控制，呈常染色体共显性遗传。它存在表型多态性，包括密度多态性和大小多态性，至少有１１种不同大小的ａｐｏ（ａ）蛋白。多态性的根本原因     

ApoE 基因多态性与中国人非胰岛素依赖型糖尿病血脂水平的关系

为研究ＡｐｏＥ基因对中国人非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者血脂水平的影响，应用聚合酶链反应（ＰＣＲ）扩增出ＡｐｏＥ基因第４外显子内的２９２ｂｐ片段，继以限制性内切酶ＨｈａⅠ酶解消化，最后行８％聚丙烯酰胺凝胶电泳，根据电泳带型判断ＡｐｏＥ基因型。共检测了１１２例非胰岛素依赖型糖尿病患者的ＡｐｏＥ基因型。通过比较不同ＡｐｏＥ基因型与血脂水平的关系发现：ＡｐｏＥ基因多态性与ＴＧ，ＨＤＬ－Ｃ，ＡｐｏＡⅠ，ＡｐｏＢ及Ｌｐ（ａ）水平无相关性，而与ＴＣ（Ｐ＝０．００２９）及ＬＤＬ－Ｃ（Ｐ＝０．００２１）水平相关，携带ε４等位基因者具有较高的ＴＣ及ＬＤＬ－Ｃ水平，而携带ε２等位基因者具有较低的ＴＣ及ＬＤＬ－Ｃ水平。     

Polymorphism insertion/deletion of apolipoprotein B gene: effect on lipid levels in obese patients

Apolipoprotein B (apoB) is the major proteic component of LDL, VLDL and chylomicrons. Numerous polymorphisms of the apolipoprotein B gene have been described. Particularly, a polymorphism of insertion/deletion located in the coding part of the signal peptide of apoB, associated with modifications of lipid concentrations and the risk of cardiovascular disease, has been reported in the general population. Since obesity is frequently associated with dyslipidemias, the aim of our study was to assess the effect of the insertion/deletion polymorphism of the apolipoprotein B gene on lipid levels in obese subjects. 234 unrelated caucasian obese subjects (74 men and 160 women, aged 39.3 +/- 10.5, BMI : 32.8 +/- 4.7) were recruited. The insertion/deletion polymorphism was determined by electrophoresis in polyacrylamide gels after PCR amplification. The relative frequencies of the Ins and Del alleles were 0.71 and 0.29 respectively. These frequencies were similar to those found in other Caucasian populations. In the whole population, individuals with the Del/Del genotype had significantly higher total-cholesterol to HDL-cholesterol ratios (p = 0.004), LDL-cholesterol to HDL-cholesterol ratios (p = 0.01) and TG-VLDL levels (p < 0.05). They also showed a tendency for higher triglyceride levels (p = 0.09) and lower HDL-cholesterol, apolipoprotein AI and LpAI levels. The allele deletion results in the absence of three amino acids (Leu-Ala-Leu) in the signal peptide of apo B. In the obese people, these structural changes may have some effect on lipid metabolism and cause variation in serum lipid concentrations.     

Influence of apolipoprotein B signal peptide insertion/deletion polymorphism on serum lipids and apolipoproteins in a Chinese population

Insertion/deletion polymorphism of the apo B gene encoding signal peptide and its influence on serum lipids and apolipoproteins was studied in 269 Chinese of both sexes in Singapore. The frequency of the Del allele was found to be 0.20, which is significantly lower than that in Caucasians (France) (0.34). The distribution of genotypes of ins/del polymorphism was at Hardy-Weinberg equilibrium in this population. There was an excess of individuals with the deletion allele in hypercholesterolemic subjects compared to those with normal cholesterol levels (P less than 0.05). All the lipid and apolipoprotein values were regressed for age, sex and BMI by multiple regression analysis. Individuals with one or two del alleles had significantly higher levels of serum total cholesterol (248.8 +/- 13.0 and 255.4 +/- 20.4 mg/dl, respectively) compared to those in individuals with only the Ins allele (218.4 +/- 7.8 mg/dl) (P less than 0.05). Serum LDL cholesterol level was also significantly higher in individuals with del allele (173.4 +/- 11.7 mg/dl) compared to that in those without the del allele (141.1 +/- 7.4 mg/dl) (P = 0.02). The percentages of sample variance of different lipid traits explained by apo B signal peptide polymorphism were estimated by analysis of variance (ANOVA) with sex, age and BMI as covariates. 2.3% of variability of serum total cholesterol (F = 3.27, P = 0.040) and 2.8% of LDL cholesterol (F = 3.87, P = 0.023) could be explained by the ins/del polymorphism of the apo B signal peptide gene.     

Interaction between SREBP-1a and APOB polymorphisms influences total and low-density lipoprotein cholesterol levels in patients with coronary artery disease

In this study, we examined the insertion/deletion (Ins/Del) and XbaI polymorphisms of the apolipoprotein B (APOB) gene and the -36delG polymorphism in the sterol regulatory element binding protein-1a (SREBP-1a) gene in 298 patients with non-diabetic angiographically assessed coronary artery disease (CAD), and 188 healthy controls, from a Brazilian population of European descent. Del/X+ haplotype carriers had higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in patients (TC, p = 0.05; LDL-C, p = 0.049) and controls (TC, p = 0.004; LDL-C, p = 0.013). No association was detected between the SREBP-1a-36delG polymorphism and lipid levels, but a significant interaction effect between APOB and SREBP-1a polymorphisms was observed in the patient sample on TC (p = 0.005) and on LDL-C (p = 0.019) levels. Carriers of the APOB Del/X+ haplotype and SREBP-1a G-G- genotype showed the highest levels of these lipid parameters. This effect of interaction was not observed in the control sample. Despite the associations with lipids, these polymorphisms were not associated with CAD risk or severity in this sample.     

载脂蛋白B基因C7673T多态与有家族聚集现象脑出血的关系

目的 探讨载脂蛋白B基因(apolipoprotein B,apo B)C7673T多态与长沙地区汉族人群有家族聚集现象脑出血的关系.方法 采用聚合酶链反应-限制性片段长度多态性分析法和DNA直接测序法检测长沙地区汉族15个有家族聚集现象脑出血家系117名成员、93例散发脑出血患者和100名正常对照者的apoB基因C7673T多态;氧化酶法测定血清甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇水平,酶联免疫吸附法测定脂蛋白(a)浓度,免疫比浊法测定apoB100及apoA Ⅰ浓度.结果 (1)家系组脑出血患者组及其Ⅰ、Ⅱ、Ⅲ级亲属组、散发脑出血组和对照组apoB基因C7673T多态T等位基因频率分别为0.176、0.136、0.058、0.048、0.081、0.040.(2)家系组脑出血患者组及其Ⅰ级亲属组apoB基因C7673T多态T等位基因频率显著高于对照组(P＜0.01,P＜0.01),而家系组Ⅱ、Ⅲ级亲属组与对照组相比差异无统计学意义(P＞0.05);家系组脑出血患者组apoB基因C7673T多态T等位基因频率显著高于散发脑出血组(P＜0.05).(3)家系组脑出血患者组及散发脑出血组中,apoB基因C7673T多态TC基因型较CC基因型的总胆固醇、低密度脂蛋白胆固醇显著增高,而高密度脂蛋白胆固醇显著降低(P＜0.05),其它指标差异无统计学意义(P＞0.05).结论 apoB基因C7673T多态T等位基因可能与长沙地区汉族人群有家族聚集现象脑出血有关;apoB基因C7673T多态T等位基因可能通过改变血脂水平影响脑出血的发生发展.     

冠心病家族史青少年载脂蛋白E、B的基因多态性

目的 探讨青少年载脂蛋白E(apolipoprotein E，apoE)、apoB基因多态性对冠心病的遗传易感性。方法 应用聚合酶链反应—限制性片段长度多态性技术，对244名健康汉族大学生(冠心病家族史阳性者109人，阴性者135人)的apoE、apoB XbaI、apoB 3’可变数目串联重复序列(variable number of tandem repeat ，VNTR)基因型进行分析。结果 阳性组的e4、x^ 、VNTR—B(hypervariable element，HVE＞38)等位基因频率显著高于阴性组(P＜0．05)，且与血总胆固醇、低密度脂蛋白—胆固醇、aPoBl00水平升高有显著相关(P＜0．05)。结论 apoE的e4、apoB Xba I的x^ 、apoB3’VNTR的VNTR—B可能为冠心病的重要遗传标记。     

汉族人群载脂蛋白(a)五核苷酸重复序列基因多态性对血脂水平的影响

目的:了解健康湖北汉族人群载脂蛋白(a)五核苷酸重复序列(pentanucleotiderepeat,PNR)基因多态性并分析其对血清脂质的影响。方法:随机选取153例健康湖北汉族受试者,测定其血清胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),载脂蛋白AI(apoAⅠ)、载脂蛋白B(apoB)及脂蛋白(a)的浓度,并采用PCR-SSCP的方法检测载脂蛋白(a)PNR基因多态性,计算各等位基因的分布频率。结果:我国汉族人群apo(a)PNR等位基因频率分布与欧美人群有显著性差异,apo(a)PNR(TTTTA)5等位基因与高Lp(a)水平相关,apo(a)PNR等位基因变异对TC、TG、HDL-C、LDL-C、ApoAI和ApoB无明显影响。结论:本研究获得了湖北健康汉族人群的血脂及apo(a)PNR等位基因分布的资料,apo(a)PNR(TTTTA)5等位基因与汉族人群高Lp(a)水平有关。     

Apolipoprotein B gene polymorphisms in ischemic heart disease and hypercholesterolemia: effects of age and sex

The association of polymorphic alleles of the apolipoprotein B gene (Insertion/Deletion-, Xbal-, MspI-, EcoRI-, and 3'-VNTR polymorphisms) with variation in lipid concentrations (total cholesterol (T-C), HDL cholesterol (HDL-C), and log-triglycerides (TG)) in plasma was studied in 259 men and 59 women with moderate hypercholesterolemia (T-C 5.5–8.0 mmol/l and TG < 2.5 mmol/l) and ischemic heart disease, especially in relation to the effect of sex and age. The XbaI and the Ins/Del polymorphic alleles were associated with variation in T-C, but only in patients below the 75th percentile for age. The XbaI and Ins/Del polymorphic alleles were synergistically associated with variation in T-C: the X+ and the Del alleles were associated with higher cholesterol concentrations. Younger male patients had the highest frequency of haplo-types including both the X+ and the Del alleles, but the most striking difference was a significantly higher frequency of haplotypes including both the X — and the Ins alleles in female and in older male patients. The heterogeneity of association of polymorphic alleles in the apolipoprotein B gene to complex traits like hypercholesterolemia and ischemic heart disease in this study could explain why in most studies the X+ allele has been associated with higher cholesterol levels, whereas the X — allele has been associated with symptomatic atherosclerosis. The results of our study emphasize the importance of age and sex in measured genotype association studies.     

浙江汉族长寿人群血脂水平及ApoB基因Xba I-RFLP和3'-VNTR多态性的相关性研究

 目的：研究浙江汉族长寿人群的血脂水平及载脂蛋白B（ApoB）基因Xba I-限制性片段长度多态性(RFLP)和3’-可变数目串联重复序列(VNTR)多态性对血脂四项和载脂蛋白水平是否有影响,了解长寿发生的机制。方法：采用体格检查与实验室研究分别对长寿老人组、长寿子女组、正常对照组和非长寿子女组进行血样采集、ApoB基因Xba I-RFLP和3'-VNTR分型。结果：血清甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）及ApoB 与长寿呈负相关（P<0.05）, 高密度脂蛋白胆固醇（HDL-C）与长寿呈正相关（P<0.01）。拥有X⁺X^-基因型的人,除TG外,TC、LDL-C及ApoB均高于拥有X^-X^-基因型的人（P<0.01）,其HDL-C低于拥有X^-X^-基因型的人（P<0.01）;拥有大等位基因的人,其TC、TG、LDL-C及ApoB均高于拥有小等位基因的人（P<0.01）,而HDL-C含量较低（P<0.01）。结论：高TG、LDL-C、ApoB和低HDL-C不利于长寿,拥有X^-X^-基因型和3'-VNTR分型小等位基因的人血脂水平较健康,也利于长寿。     

难治性肾病综合征患儿载脂蛋白E基因多态性的研究

目的：研究难治性肾病综合征（steroid-resistant idiopathic nephrotic syndrome,SRINS)患儿载脂蛋白E基因多态性,为临床上正确选择合适的脂质代谢紊乱病例进行降脂治疗提供依据。方法：用酶法测定了60例SRINS患儿及80例健康儿童血脂、脂蛋白、载脂蛋白3种物质共7个脂质代谢指标,用PCR－SSCP法检测载脂蛋白E（apoE)基因型,并行肾穿刺活检术检查肾病综合征患儿病理类型。结果：SRINS患儿存在明显脂质紊乱,与健康儿童比较差异有显著性（P＜0．01）,随诊半年后仍有绝大多数SRINS患儿存在明显脂质代谢紊乱。难治性肾病综合征apoε2等位基因显著多于健康儿童（P＜0．05）。结论：SRINS患儿脂质代谢紊乱持续的时间较长,这类患儿,尤其携带ε2等位基因者,更易发生进行性肾脏损害,动脉粥样硬化及冠心病。应考虑给这类患儿使用降脂药物。     

Association between apolipoprotein E polymorphism and serum lipid and apolipoprotein levels with Alzheimer's disease

We have recently demonstrated that apolipoprotein E (APOE)-varepsilon4 allele is a risk factor for Alzheimer disease (AD) in Tehran, Iran. The current study specifically aimed to examine whether APOE polymorphism in association with serum lipids-apolipoprotein level is a risk factor for AD in a population from Tehran, Iran. APOE polymorphism and plasma lipids, apoA1, apoB and lipoprotein (a) (Lp(a)) levels were determined in 94 AD patients and 111matched controls. Our study demonstrated a significant association between APOE polymorphism and the level of plasma lipids and apolipoprotein with AD in this population. The AD subjects had significantly lower apoA1 (p<0.001) and HDL-C (p<0.01) and higher apoB (p=0.01) and LDL-C (p=0.02) levels than that of the control group. The AD subjects carrying APOE-varepsilon4 allele had lower plasma apoA1 (t=5.2, p<0.002) and HDL-C level (t=2.7, p=0.01) but had higher plasma apoB (t=-5.4, p<0.002), LDL-C (t=-4.6, p=0.005) and total cholesterol (TC) (t=-2.7, p=0.01) than that of the non APOE-varepsilon4 carriers. These results indicated that AD patients with APOE-varepsilon4 allele has a distinct plasma lipid profile and carrier of this allele with low levels of apoA1 and HDL-C may be more susceptible to AD.