胰岛素对THP—1细胞脂蛋白脂酶mMA表达及细胞泡沫化的影响

目的：观察胰岛素在氧化低密度脂蛋白(ox—LDL)致人髓系白血病单核细胞株THP—1细胞泡沫化过程中的作用，并探讨其机理。方法：用不同浓度胰岛素及ox—LDL与THP-1细胞一起共同孵育，观察：THP—1细胞脂蛋白脂酶(LPL)mRNA RT—PCR产物、非特异性脂酶染色THP—1细胞所得脂酶阳性细胞数、细胞大小变化、油红O染色所得含脂滴细胞数、细胞内胆固醇含量。结果：100mU/L以上浓度胰岛素各组：THP—1细胞LPL mRNA表达与oox—LDL对照组比较上调2倍；细胞周长、脂滴阳性细胞百分率及细胞内胆固醇含量均明显高于ox—LDL对照组(P＜0．05)。结论：高浓度胰岛素在ox—LDL存在条件下有促进THP—1细胞向泡沫细胞转化的作用，其机理可能与细胞LPL mRNA表达上调有关。     

山荷减肥颗粒对饮食诱导肥胖大鼠瘦素、脂联素、抵抗素的影响

目的： 观察山荷减肥颗粒对高脂饮食诱导的肥胖模型大鼠的减肥降脂作用及对脂肪组织脂联素、抵抗素基因表达的影响。方法： 肥胖模型大鼠随机分为山荷减肥颗粒高、中、低剂量3个实验组及高脂对照组、正常组。对给药8周的动物称体重,测体长,计算Lees指数,测定大鼠血清胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）及高密度脂蛋白（HDL）的水平,用ELISA法测瘦素水平,用RT-PCR 检测附睾周围脂肪组织脂联素、抵抗素mRNA 表达。结果：山荷减肥颗粒组大鼠体重、Lees指数、脂肪重量、血清TC、TG、LDL水平明显低于高脂组大鼠（P<0.05）,瘦素明显低于高脂模型组（P>0.05）,脂肪组织脂联素、抵抗素mRNA的表达水平明显高于高脂组大鼠（P<0.05）。结论：山荷减肥颗粒对肥胖大鼠具有减肥降脂作用,调整肥胖大鼠脂肪组织瘦素、脂联素、抵抗素mRNA的表达水平,可能是其治疗肥胖的作用机制之一。     

脂筏与病毒感染

脂筏是质膜上具有低流动性,呈现有序液相,富含胆固醇和鞘磷脂的特殊膜结构。与糖基磷脂酰肌醇（GPI）相连,或被肉豆蔻酸酰化是脂筏分子主要的两种蛋白修饰形式。膜上许多结构可通过被GPI锚固的形式作为细菌、病毒以及毒素的受体。脂筏介导质膜的内吞作用、病毒颗粒的装配及出芽过程以及跨膜信号传导等重要的生物学过程。     

胆固醇酯转运蛋白基因Taq Ⅰ B多态性与蒙古族原发性高血压的相关性

目的 分析胆固醇脂转移蛋白（CETP）基因TaqⅠB多态性与蒙古族人群原发性高血压（EH)的关系。方法 从内蒙古自治区通辽市蒙古族健康体检人群随机抽取1819例,其中高血压组（840例）,正常血压组（979例）进行病例-对照研究。用多聚酶链式反应/限制性片段长度多态性(PCR-RFLP)及直接测序方法鉴定CETP基因的TaqⅠB多态性位点基因型。结果 TaqⅠB位点GG,GA,AA基因型和G/A等位基因频率分布在整个人群,男性组和女性组中均符合Hardy-Weinberg遗传平衡。无论在整体人群还是按性别分组的亚群中,原发性高血压组CETP基因TaqⅠB位点GG,GA,AA基因型和G/A等位基因频率分布和对照组无差异。在男性组中,与携带CETP基因TaqⅠB位点GG基因型的个体相比,AA型个体的高密度脂蛋白胆固醇水平显著升高,总胆固醇和甘油三酯水平显著降低（P＜0.05）。结论 CETP基因TaqⅠB多态性不是原发性高血压的直接危险因素,但可影响血脂水平,可能间接参与原发性高血压的发生。     

北京市西城区中老年人群脂蛋白脂酶基因多态性与高脂血症关系的研究

目的 了解脂蛋白脂酶（lipoprotein lipase,LPL）基因PvuⅡ位点多态性在人群中的分布情况及其与高脂血症的关系。方法 选高西城区179例高脂血症患者作为病例组，同时选择136名血脂正常者作为对照组，对所有对象均进行血脂谱项目测定及LPL－PvuⅡ位点多态性检测（聚合酶链反应－限制性片段长度多态性方法）。结果 LPL基因PvuⅡ位点（＋／＋）、（＋／－）及（－／－）基因型的构成比分别为40.3%,47.9%和11.7%，（－）等位基因的频率分别为35.7%；高胆固醇血症及高甘油三酯血症（－）等位基因携带者的构成比明显低于对照组（P＜0.05）;且（－）等位基因携带者TG水平低于（＋）等位基因携带者因携带者的构成比明显低于对照组（P＜0.05）；且（－）等位基因携带者TG水平低于（＋）等位基因携带者（P＞0.05）。结论 LPL基因PvuⅡ位点基因多态性与中老年人群高脂血症相关，（－）等位基因与胆固醇、甘油三酯水平降低有关。     

脂蛋白脂酶Ser447Ter基因多态性与动脉硬化性脑梗死的相关研究

目的研究脂蛋白脂酶（lipoprotein lipase，LPL）Ser447Ter基因多态性与动脉粥样硬化性脑梗死（atherosclerotic cerebral infarction, CI）发病的关系及其对血脂水平、颈动脉斑块的影响。方法对166例CI患者及72名健康成人采用聚合酶链反应-限制性片段长度多态性方法检测LPL-Ser447Ter基因多态性，颈动脉超声多普勒检查颈总动脉内膜中层厚度（intima-media thickness，IMT）和颈动脉斑块（carotid artery plaque，CAP）的形状及大小。结果CI组CG＋GG基因型甘油三酯（triglyceride，TG）含量比CC基因型明显降低（P=0．1301），高密度脂蛋白胆固醇（high density lipoprotein cholesterol，HDL-C）含量明显增高（P=0．007）；对照组CG＋GG基因型TG含量比CC基因型低（P=0．041）；CI组G等位基因频率低于对照组（P=0．014）；LPLSer447Ter基因多态性与颈总动脉IMT和CAP分级无明显相关。结论LPL Ser447Ter基因多态性与血脂变化及脑梗死的关系密切，G等位基因可能引起血TG降低、HDL-C升高；G等位基因可能是脑梗死的保护基因型．     

ApoE^-/-母体孕期高脂高胆固醇饮食对子代成年鼠动脉粥样硬化的影响

目的研究母体孕期高脂高胆固醇饮食对子代成年鼠动脉粥样硬化的发生影响。方法ApoE^-/-孕鼠分为高脂高胆固醇饮食组（G组）和普通饮食组（P组）,G组雄性子代成年鼠分为高脂高胆固醇饮食组（G—G）和普通饮食组（G—P）,P组子代雄性成年鼠继续喂养普通饲料（P—P）,60d后检测子代成年鼠总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）和低密度脂蛋白（LDL）浓度,HE染色观察血管形态学变化及动脉粥样硬化（atherosclerosis,AS）斑块形成情况。结果G—G组和G—P组的TC、TG、LDL和HDL浓度较P—P组明显升高,且与P—P组相比Tc浓度存在显著性差异（P〈0．05）,TG、LDL和HDL浓度存在极显著性差异（P〈0．01）;P—P组无AS斑块形成,G—G组与G．P组均有AS斑块形成,前者斑块形成率及斑块面积与血管管腔面积之比（PA／LA）都高于后者,两组PA／LA存在极显著性差异（P〈0．01）。结论母体孕期高脂高胆固醇饮食对子代成年鼠动脉粥样硬化的发生具有重要影响。     

低密度脂蛋白,高脂血清对内皮细胞膜脂流动性的影响

实验用DPH荧光偏振技术测定经人低密度脂蛋白(LDL)及兔高脂血清(HRS)孵育的牛主动脉内皮细胞(EC)的膜脂微粘度。结果表明LDL孵育EC12小时导致细胞膜脂流动性下降,过氧化脂质(Lpo)含量增高;EC经HRS作用36小时后也发生相似的变化。形态观察证明EC胞浆中有大量脂滴样结构。结果提示高胆固醇含量的LDL和HRS可能通过增加膜的胆固醇含量而降低膜的流动性,高浓度Lpo可能也起重要作用。     

胰岛素对THP-1细胞脂蛋白脂酶 mRNA表达及细胞泡沫化的影响

目的 观察胰岛素在氧化低密度脂蛋白(ox-LDL)致人髓系白血病单核细胞株THP-1细胞泡沫化过程中的作用,并探讨其机理.方法 用不同浓度胰岛素及ox-LDL与THP-1细胞一起共同孵育,观察THP-1细胞脂蛋白脂酶(LPL) mRNA RT-PCR产物、非特异性脂酶染色THP-1细胞所得脂酶阳性细胞数、细胞大小变化、油红O染色所得含脂滴细胞数、细胞内胆固醇含量.结果 100 mU/L以上浓度胰岛素各组THP-1细胞LPL mRNA表达与ox-LDL对照组比较上调2倍;细胞周长、脂滴阳性细胞百分率及细胞内胆固醇含量均明显高于ox-LDL对照组(P＜0.05).结论 高浓度胰岛素在ox-LDL存在条件下有促进THP-1细胞向泡沫细胞转化的作用,其机理可能与细胞LPL mRNA表达上调有关.     

脂筏与病毒感染

脂筏是质膜上具有低流动性,呈现有序液相,富含胆固醇和鞘磷脂的特殊膜结构。与糖基磷脂酰肌醇(GPI)相连,或被肉豆蔻酸酰化是脂筏分子主要的两种蛋白修饰形式。膜上许多结构可通过被GPI锚固的形式作为细菌、病毒以及毒素的受体。脂筏介导质膜的内吞作用、病毒颗粒的装配及出芽过程以及跨膜信号传导等重要的生物学过程。     

Effect of pravastatin on metabolic parameters of apolipoprotein B in patients with mixed hyperlipoproteinemia

Summary 3-Hydroxy-3-methylgluratyl coenzyme A reductase inhibitors reduce plasma cholesterol in different forms of hyperlipoproteinemia. Although an increase in low-density lipoprotein (LDL) receptor activity is the proven mechanism of this therapy in familial hypercholesterolemia, the mechanism remains controversial in mixed hyperlipoproteinemia. A decreased production of apolipoprotein B (apoB) and/or an increased removal of lipoproteins could mediate the hypocholesterolemic effect of these drugs. The effect of pravastatin on the metabolism of apoB was evaluated in a randomized, double blind, placebo controlled, cross-over study in five men with mixed hyperlipoproteinemia. Metabolic parameters for apoB were determined using endogenous labeling with [1^t3C]leucine and [¹⁵N]glycine and multicompartmental modeling. During pravastatin therapy cholesterol, LDL cholesterol, apoB, and LDL apoB levels were significantly reduced (P < 0.01) by 18%, 20%, 27%, and 29%, respectively, while triglyceride and high-density lipoprotein cholesterol levels remained unchanged. Pravastatin therapy increased the fractional catabolic rate of very low density lipoprotein apoB from 3.9±0.6 to 5.1±1.7 per day (P = 0.08) and that of LDL apoB from 0.37±0.09 to 0.46±0.10 per day (P<0.01). The apoB production (placebo 35.2±11.9 mg/kg per day; pravastatin 25.8±8.7 mg/kg per day) and conversion of very low density lipoprotein apoB to LDL apoB (placebo 65%, pravastatin 57%) remained stable. Thus, also in mixed hyperlipoproteinemia 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase the catabolism of apoB-containing lipoproteins without significantly affecting the production of apoB.Abbreviations apoB apolipoprotein B - FCR fractional catabolic rate - HMG hydroxy-methylglutaryl - CoA coenzyme A - FH familial hypercholesterolemia - HDL high-density lipoprotein - IDL intermediate-density lipoprotein - LDL low-density lipoprotein - VLDL very low density lipoprotein Dedicated to Prof. Dr. G. Paumgartner on the occasion of his 60th birthday     

Why is non−high-density lipoprotein cholesterol a better marker of the risk of vascular disease than low-density lipoprotein cholesterol?

Low-density lipoprotein cholesterol (LDL-C) has been the focus of managing lipoprotein disorders for decades. It is now time to consider a change. Both apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (HDL-C) have been shown to be more accurate markers of cardiovascular risk than LDL-C. ApoB measures total atherogenic particle number, of which 90% are LDL particles. Therefore, LDL particle number determines plasma apoB in most patients. Non-HDL-C is widely assumed to be superior to LDL-C when triglyceride concentrations are elevated (even modestly) because it includes the cholesterol in very-low-density lipoprotein. However, evidence does not support this concept. Rather, non-HDL-C appears to be an indirect way of estimating apoB. We argue that we should integrate the information from non-HDL-C and apoB for better risk assessment and a better target of therapy.     

Xbal polymorphism in DNA at the apolipoprotein B locus is associated with myocardial infarction (MI)

Bøhn M, Bakken A, Erikssen J, Berg K. Xbal polymorphism in DNA at the apolipoprotein B locus is associated with myocardial infarction (MI). Clin Genet 1993: 44: 241–248. © Munksgaard, 1993 High levels of low density lipoprotein (LDL) and its apolipoprotein B (apoB) are risk factors for atherosclerosis and myocardial infarction (MI). There is rich genetic polymorphism in apoB, first detected as the Ag allotypes of LDL, but today mostly examined at the DNA level. Genes contribute to the population variation in LDL and apoB levels and alleles in polymorphisms at the apoB locus are candidate genes with respect to control of lipid levels and susceptibility to atherosclerosis and MI. The Xbal polymorphism at the apoB locus, which involves the third base of threonin codon 2488 (ACC→ACT) without changing the amino acid sequence was examined in a case-control study comprising 238 survivors of myocardial infarction (MI) and 621 controls. In univariate analysis, frequencies of genotypes in this polymorphism were not statistically different between patients and controls of either sex. However, in multivariate logistic regression analysis, the odds ratio X - X - homozygotes (homozygotes for absence of restriction site) for having MI compared to the pooled group of heterozygotes and X + X + homozygotes (homozygotes for presence of restriction site) was 2.16 (p = 0.007), after adjustments for age, sex, and levels of apoB, high density lipoprotein (HDL) cholesterol (HDLC) and Lp(a) lipoprotein. It appeared that heterozygotes do not have increased risk, compared to the X + X + homozygotes. Stratification according to low or high levels of apoB, HDLC and Lp(a) lipoprotein, showed that the X - X - genotype was more common in patients than controls, in all subgroups. We conclude that the X - allele in double (but not in single) dose most probably increases the risk of MI. The increased risk is apparently not conferred by higher levels of total cholesterol, LDL or apoB, but through some variable or mechanism not closely related to traditional risk factors.     

Apolipoprotein B100 quality control and the regulation of hepatic very low density lipoprotein secretion

Apolipoprotein B (apoB) is the main protein component of very low density lipoprotein (VLDL) and is necessary for the assembly and secretion of these triglyceride (TG)-rich particles. Following release from the liver, VLDL is converted to low density lipoprotein (LDL) in the plasma and increased production of VLDL can therefore play a detrimental role in cardiovascular disease. Increasing evidence has helped to establish VLDL assembly as a target for the treatment of dyslipidemias. Multiple factors are involved in the folding of the apoB protein and the formation of a secretion-competent VLDL particle. Failed VLDL assembly can initiate quality control mechanisms in the hepatocyte that target apoB for degradation. ApoB is a substrate for endoplasmic reticulum associated degradation (ERAD) by the ubiquitin proteasome system and for autophagy. Efficient targeting and disposal of apoB is a regulated process that modulates VLDL secretion and partitioning of TG. Emerging evidence suggests that significant overlap exists between these degradative pathways. For example, the insulin-mediated targeting of apoB to autophagy and postprandial activation of the unfolded protein response (UPR) may employ the same cellular machinery and regulatory cues. Changes in the quality control mechanisms for apoB impact hepatic physiology and pathology states, including insulin resistance and fatty liver. Insulin signaling, lipid metabolism and the hepatic UPR may impact VLDL production, particularly during the postprandial state. In this review we summarize our current understanding of VLDL assembly, apoB degradation, quality control mechanisms and the role of these processes in liver physiology and in pathologic states.     

Lipids and HCV

Chronic hepatitis C virus (HCV) infection is associated with an increase in hepatic steatosis and a decrease in serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL) and apolipoprotein B (apoB), the main protein constituent of LDL and very low-density lipoprotein (VLDL). These changes are more marked in HCV genotype 3 infection, and effective treatment results in their reversal. Low lipid levels in HCV infection correlate not only with steatosis and more advanced liver fibrosis but also with non-response to interferon-based therapy. The clinical relevance of disrupted lipid metabolism reflects the fact that lipids play a crucial role in the life cycle of hepatitis C virus. HCV assembly and maturation in hepatocytes depend on microsomal triglyceride transfer protein and apoB in a manner that parallels the formation of VLDL. VLDL production from the liver occurs throughout the day with an estimated 10¹⁸ particles produced every 24 h whilst the estimated hepatitis C virion production rate is 10¹² virions per day. HCV particles in the serum exist as a mixture of complete low-density infectious lipo-viral particles (LVP) and a vast excess of apoB-associated empty nucleocapsid-free sub-viral particles that are complexed with anti-HCV envelope antibodies. Apolipoprotein E (apoE) is also involved in HCV particle morphogenesis and is an essential apolipoprotein for HCV infectivity. ApoE is a critical ligand for the receptor-mediated removal of triglyceride rich lipoprotein (TRL) remnants by the liver. The dynamics of apoB-associated lipoproteins, including HCV-LVP, change post-prandially with an increase in large TRL remnants and very low density HCV-LVP which are rapidly cleared by the liver (at least three HCV receptors are cellular receptors for uptake of TRL remnants). In summary, HCV utilises triglyceride-rich lipoprotein pathways within the liver and the circulation to its advantage.     

Lipoproteins in human atherosclerotic vessels. I. Biochemical properties of arterial low density lipoproteins, very low density lipoproteins, and high density lipoproteins.

Lipoproteins extracted from the human aortic intima into 1.65 M NaCl were quantitated and characterized biochemically and by electron microscopy following separation in the preparative ultracentrifuge. The arterial lipoproteins, although separated and designated according to the density classes used for the serum lipoproteins, were distinctly different from their serum counterparts. The amount of lipoproteins in the low density range of d 1.063 to 1.006 (arterial LDL) and in the very low density range of d < 1.006 (arterial VLDL) extracted from arterial intima increased with increasing intimal lipid content. In contrast, the concentration of lipoproteins in the high density range of d 1.210 to 1.063 (arterial HDL) was small and did not change with the severity of atherosclerosis.Arterial VLDL, LDL and its subfractions, LDL₁ (d 1.006 to 1.019) and LDL₂ (d 1.019 to 1.063), were markedly heterogenous and contained unusually large particles, which were isolated by Bio-Gel A-150. These particles showed a pitted and cratered appearance by scanning electron microscopy and were immunochemically unreactive and had no electrophoretic mobility. The lipid and amino acid composition of the arterial VLDL and LDL fractions as well as their electrophoretic, chromatographic and analytical flotation behavior was distinctly different from that of their serum lipoprotein counterparts. Arterial VLDL, in sharp contrast to serum VLDL, was rich in cholesteryl ester and poor in triglycerides. Arterial VLDL also showed no electrophoretic mobility and only half of the preparations reacted to LDL antisera. Acid mucopolysaccharides were detected in the arterial VLDL and LDL fractions in association with the large size particles which lacked electrophoretic mobility and immunochemical reactivity and showed only a “saw tooth” pattern in the analytical ultracentrifuge. Arterial LDL and LDL₂ contained a smaller sized population of particles as separated by Bio-Gel A-150. These particles exhibited a reaction of complete identity with serum LDL when reacted against LDL antiserum. However these particles had a greater electrophoretic mobility and different amino acid composition than did serum LDL and LDL₂. An asymmetrical peak with a mean SF of 7.3 was demonstrated by these particles in the analytical ultracentrifuge.The over-all studies suggest that lipid deposition in atherosclerotic plaques is associated with the accumulation of lipoproteins with biochemical and ultrastructural properties unlike those of serum lipoproteins. The presence of these lipoproteins in the arteries may be a result of the interaction of serum and arterial lipoproteins with acid mucopolysaccharides and of lipoprotein synthesis and degradation in the arteries.     

Reduction of lp(a) by different methods of plasma exchange

Summary Lipoprotein(a) has been shown to be an independent risk factor for atherosclerosis. The effect of different forms of plasmapheresis therapy on the removal ofLp (a) is examined. Plasmapheresis is successfully administered in a small number of hypercholesteremic patients who fail to respond to conventional therapy. Comparison of four different methods of plasma exchange (albumin substitution, anti-apoB antibody column, LDL precipitation, filtration) reveals significant differences in effectiveness in the ability to lower plasma Lp(a): plasma exchange with albumin und LDL precipitation seem to be the most effective, plasma filtration the least.Abbreviations Lp(a) lipoprotein(a) - LDL low density lipoprotein - HDL high density lipoprotein - VLDL very low density lipoprotein - DEAE diethylaminoethyl - SD standard deviation - HELP heparin induced extracorporal LDL precipitation - RCA right coronary artery - LAD left anterior descendent coronary artery - AOCB aortocoronary bypass - MI myocardial infarction - apoB apolipoprotein B     

Increased plasma levels of LDL cholesterol in rabbits after adenoviral overexpression of human scavenger receptor class B type I

Scavenger receptor class B type I (SR-BI), a CD36 family member, plays a key role in high-density lipoprotein (HDL) metabolism, reverse cholesterol transport, and whole body cholesterol homeostasis, and is shown to be involved in the development of atherosclerosis in mice. In this report, we describe the effects of the adenoviral overexpression of human SR-BI (hSR-BI) in New Zealand White (NZW) rabbits, a wild-type animal model that expresses cholesteryl ester transfer protein (CETP) in plasma, displays a manlike lipoprotein profile, and is susceptible to atherosclerosis. A total of 1×10¹² adenoviral particles containing either hSR-BI or lacZ complementary deoxyribonucleic acid (control) were infused into the ear vein of NZW rabbits. Transgene expression was ascertained by TaqMan Real Time polymerase chain reaction measurements. Rabbits infected with Ad/hSR-BI (adenoviral plasmids containing hSR-BI) showed a faster clearance of administered [³H]HDL cholesterol and significantly decreased apolipoprotein (apo) A-I levels when compared to control rabbits, respectively. Interestingly, we found markedly increased levels of low-density lipoprotein (LDL) cholesterol exclusively in SR-BI-overexpressing rabbits. These changes were not accompanied by alterations in LDL receptor expression but by increased levels of CE transfer in these animals. By lowering HDL cholesterol and increasing plasma apoB-containing lipoprotein levels, the overexpression of SR-BI leads to a lipoprotein pattern, which is believed to enhance the development of atherosclerosis. The role of SR-BI in lipoprotein metabolism and atherogenesis in rabbits—a CETP-expressing animal model displaying a manlike lipoprotein profile—may therefore be different from the one found in rodents.     

脂蛋白（a）在主动脉粥样硬化病变中的定位与定量研究

脂蛋白（ａ）［Ｌｉｐｏｐｒｏｔｅｉｎ（ａ），Ｌｐ（ａ）］是动脉粥样化中的独立危险因子，我们采用免疫组织化学技术、免疫电镜技术、酶联免疫吸附法及图像分析技术，研究了正常及不同程度动脉粥样硬化病变的尸检主动脉中Ｌｐ（ａ）分布的量及形式。结果显示：动脉粥样硬化血管壁Ｌｐ（ａ）含量显著增高，各不同病变区域Ｌｐ（ａ）有其独特的分布规律，Ｌｐ（ａ）主要位于细胞外基质中，只在少数泡沫细胞内才发现有Ｌｐ（ａ）。Ａ     

Genetic influences contributing to LDL particle size in familial combined hyperlipidaemia

The nature of the genetic and environmental factors influencing low density lipoprotein (LDL) particle size in patients with familial combined hyperlipidaemia (FCHL) is under debate. We measured LDL peak particle size in 553 subjects belonging to 48 Finnish FCHL families. Individuals with high triglyceride (TG) concentrations (phenotype IV) or combined hyperlipidaemia (phenotype IIB) had significantly smaller LDL particles than those with hypercholesterolaemia (phenotype IIA) or unaffected subjects (P<0.001). In stepwise regression analyses, serum TGs (r(2)=43%, P<0.001) and high density lipoprotein cholesterol (HDL-C) (r(2)=4.5%, P<0.001) were the only significant predictors of LDL peak particle size. Familial correlations support the conclusion that LDL peak particle size is familial, and most probably influenced by genes in these families. Segregation analysis of LDL peak particle size, a quantitative trait, was performed to model this genetic influence. Our results suggest a polygenic background for LDL size with a recessive major gene that may contribute to large LDL peak particle size in women. Serum TG and HDL-C concentrations predict the majority of variations in LDL particle size.