脂蛋白脂酶基因S447X及HindⅢ位点多态性与冠心病的关系

目的:探讨脂蛋白脂酶(LPL)基因S447X及HindⅢ多态性与冠心病的关系.方法:对249例经冠状动脉造影证实为冠心病的患者及167例经冠状动脉造影证实无冠状动脉病变的对照者进行研究,采用酶法测定血脂各项水平,采用多聚酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)分析LPL基因中S447X及HindⅢ多态性.结果:冠心病组与对照组比较,LPL S447X及HindⅢ基因型及等位基因分布频率均无显著性差异,P＞0-05.而按血浆TG水平分组可见低TG组(TG＜1.7mmol/L)的SX/XX基因型频率及X等位基因频率均明显高于高TG组(TG≥1.7mmol/L),P＜0.05.且低TG组中SX/XX基因型与SS基因型比较各项血脂水平(sLDL除外)均有显著性差异,P＜0.05.结论:S、X、H 、H-等位基因频率在冠心病组及对照组之间无明显差异.LPLS447X及HindⅢ多态性并不是冠心病发病的独立危险因素,但S447X变异由于对血脂代谢产生了有益的影响(TC、TG、LDL-C、sLDL、VLDL-C及ApoB水平均降低,HDL-C升高)因而可被认为是冠心病的保护因素之一.     

妊娠期高血压疾病患者胎盘组织中ApoE、LPL ser447stop基因多态性检测及意义

目的检测妊娠期高血压疾病(HDP)患者胎盘组织中载脂蛋白E(ApoE)及脂蛋白脂酶(LPL)第9外显子(ser447stop)基因多态性,并探讨其临床意义。方法采用multi-ARMS PCR及PCR-RFLP方法,分别检测36例妊娠期高血压患者(A组)、94例子痫前期患者(B组)及130例正常妊娠妇女(C组)胎盘组织中的ApoE及LPLser447stop基因多态性。结果 A组ApoE2/3、E2/4、E3/3、E3/4及E4/4基因表型频率分别为25.00%、0、50.00%、22.22%、0,B组分别为19.15、0、56.38、24.47%、1.06%,C组分别为14.61%、3.08%、76.92%、5.38%、0.77%。A、B组E3/3、E3/4基因型与C组比较,P均<0.01。A组ApoE等位基因ε2、ε3、ε4频率分别为12.50%、73.61%、11.11%,B组分别为9.57%、78.19%、13.30%,C组分别为8.46%、86.54%、5.00%。A、B组ApoE等位基因ε3、ε4与C组比较,P均<0.05。共检测到3例LPL ser447stop杂合子变异,其中B组2例,C组1例。各组间比较,P均>0.05。结论 HDP患者胎盘组织中ApoE3/4基因表型、ApoEε4等位基因频率增高,ApoEε3等位基因频率降低;ApoE3/4基因表型可能是HDP的危险因素,ApoEε4等位基因可能是HDP的遗传易患因子,而ApoEε3等位基因则具有保护作用。LPL ser447stop基因多态性可能与HDP的发生无关。     

富含甘油三酯脂蛋白代谢及其在动脉粥样硬化中的作用

甘油三酯(TG)主要存在于富含甘油三酯脂蛋白(TRLs)中,TRLs代谢失调与动脉粥样硬化发生发展密切相关。脂蛋白脂酶(LPL)是一种由实质细胞分泌的糖蛋白,可将TRLs中的TG分解为游离脂肪酸。许多因子通过调控LPL表达与活性影响TRLs代谢及动脉粥样硬化进程。因此,阐明TRLs代谢及调控机制对于心血管疾病防治具有重要意义。     

Lipoprotein lipase in relation to inflammatory activity in rheumatoid arthritis

Objective. To evaluate the impact of chronic inflammation on lipoprotein lipase (LPL) levels and triglyceride metabolism in patients with rheumatoid arthritis (RA). Design. Plasma levels of LPL activity and mass before and after heparin were determined in post-menopausal women with active RA and in controls. The results were related to lipid levels and inflammatory variables. The LPL activity and mass together with triglyceride levels were also measured before and 6 h after an oral fat load. Setting. The study was performed on in- and out-patients at a University Rheumatology clinic. The controls came from the same reference area. Subjects. Altogether 17 consecutive post-menopausal female patients with RA and 16 age and sex matched controls were enrolled for the initial determination of LPL. Fifteen of the patients and 15 of the controls agreed to take part in the fat load. Of these, one patient and one control were excluded. Main outcome measures. LPL determination: basal levels and post-heparin levels of LPL activity and mass. Correlations between LPL and blood lipids (cholesterol, triglycerides), lipoprotein levels (high density lipoprotein, HDL; low density lipoprotein, LDL), erythrocyte sedimentation rate (ESR) acute phase proteins (orosomucoid, haptoglobin, fibrinogen mass) and cytokines (tumour necrosis factor α, TNF-α; interleukin 1β, IL-1β; and interleukin-6, IL-6). Fat tolerance test: LPL activity, mass and triglyceride levels before and 6 h after a per oral fat load. Results. Pre-heparin LPL mass (P<0.01) and activity (P<0.01) were significantly lower in the rheumatoid patients. Pre-heparin LPL mass showed no correlation to the lipid levels, but an inverse correlation to several inflammatory parameters; it was significant for orosomucoid (r_s=?0.63, P<0.05) and C-reactive protein (CRP) (r_s=?0.54, P<0.05) and close to significant for haptoglobin (r_s=?0.48, P=0.087) and IL-6 (r_s=?0.52, P=0.061). Six hours after a lipid load the LPL activity and mass were significantly lower in RA (P<0.05 and P<0.01, respectively) but the triglyceride level was not significantly different compared to controls. Conclusion. An inverse relationship exists between inflammatory status and pre-heparin LPL mass. Pre-heparin LPL mass reflects mainly the inactive monomeric fraction of LPL. This has been shown to hinder the uptake of remnant lipoprotein particles through competition with lipoprotein bound dimeric LPL for the LDL receptor-related protein (LRP receptor) on hepatocytes and macrophages in culture. A decrease of the level of monomeric LPL in plasma may thus be beneficial for remnant catabolism. The same mechanism may on the other hand increase macrophage uptake of lipids. This may not affect global lipid metabolism but may be important in driving the atherosclerotic process in the vessel wall.     

Lipoprotein pattern and plasma lipoprotein lipase activities in patients with primary biliary cirrhosis

Plasma lipids, apoprotein A-I and B in serum and in lipoprotein fractions (VLDL + LDL, HDL₂, and HDL₃) obtained by preparative ultracentrifugation, as well as postheparin lipoprotein lipase activity (H-TGL and LPL) were evaluated in 17 subjects with primary biliary cirrhosis (stage II and III) subdivided into two groups according to the presence or absence of lipoprotein X (Lp-X). A reduction in total lipoprotein lipase activity was observed in both patient groups, compared to controls (P<0.01); the hepatic lipoprotein lipase was significantly reduced (P<0.01) only in the Lp-X-positive group. The lipid (477.8+154.3 vs 239.6±51.1; P<0.01) and protein (147.4±37.1 vs 83.3±19.7; P< 0.01) masses in the VLDL + LDL fraction of the Lp-X-positive group were increased compared to controls. In the same group, the HDL₂ fraction also showed an increase in lipid (186.6±80.0 vs 77.9±21.6; P<0.01) and protein (133.9±60.0 vs 67.9±16.5; P <0.01) masses; in addition, the HDL₂ percent lipid composition was different in the two patient groups, showing a decrease in esterified cholesterol (20.4±3.6 vs 25.7±2.2; P <0.01) and an increase in phospholipids (59.2±2.9 vs 54.8±2.6; p<0.01) in the Lp-X-positive group. Apo B was also increased in Lp-X-positive patients both in the serum (134.0±27.6 vs 90.9±7.3; P<0.01) and in the VLDL + LDL fraction (134.0±22.2 vs 72.5±16.5; P<0.01). The differences seen in lipoprotein concentration and composition in the two patient groups seem related, in part, to the presence of Lp-X or, better, to the stage of the disease. The reduction in hepatic lipase may play an important role in determining the increase and altered composition of the HDL₂ subfraction.     

脂蛋白脂酶基因多态性与冠心病关系的初探

目的探讨脂蛋白脂酶（ＬＰＬ）基因多态性与冠心病的关系。方法选择１０６例住院存活的心肌梗塞病人按１∶１进行病例对照研究，采用条件Ｌｏｇｉｓｔｉｃ回归分析。结果吸烟、ＬＰＬ基因型ＰＶＵⅡ（－－）和单倍体基因型Ｈ＋Ｐ－是冠心病独立的危险因素；高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）和载脂蛋白（Ａｐｏ）Ａ／Ｂ比值是冠心病的保护因素。去除其它因素的影响后，ＬＰＬＰＶＵⅡ（－－）／非（－－）和Ｈ＋Ｐ－／非Ｈ＋Ｐ－的ＯＲ值为１７．１８和３．６７；ＨＤＬ－Ｃ、ＡｐｏＡ／Ｂ比值的ＯＲ值在模型Ａ和Ｂ中分别为０．１４、０．１５和０．０４、０．０９。结论除传统的危险因素外，ＬＰＬ基因型ＰＶＵⅡ（－－）和单倍体Ｈ＋Ｐ－可能是易患冠心病的遗传标志；ＨＤＬ－Ｃ、ＡｐｏＡ／Ｂ比值可能是较其它血脂指标更好的冠心病独立预测因素     

Response of adipose tissue lipoprotein lipase activity and serum lipoproteins to acute hyperinsulinaemia in man

Summary In order to assess the short-term effects of hyperinsulinaemia and hyperglycaemia on adipose tissue lipoprotein lipase activity and on serum lipoproteins, we measured these variables in ten normal subjects during euglycaemic and hyperglycaemic hyperinsulinaemic clamps. The mean steady-state plasma glucose and insulin concentrations, respectively, were 4.7 mmol/l and 101 mU/l during euglycaemic moderate-insulin clamp, 4.9 mmol/l and 565 mU/l during euglycaemic high-insulin clamp, and 8.8 mmol/l and 148 mU/l during hyperglycaemic clamp. Saline infusion was used as control. The adipose tissue lipoprotein lipase activity rose significantly over 5 h during high-insulin clamp (p<0.01) and during hyperglycaemic clamp (p<0.05), but did not change during the moderate-insulin clamp. The magnitude of change of lipoprotein lipase activity from baseline (either rise or fall) was inversely related to the preclamp activity during euglycaemic moderate-insulin clamp (r= -0.67), during hyperglycaemic clamp (r= -0.68) and during infusion of saline (r= -0.75, p<0.05). Total serum triglyceride concentration decreased significantly during all clamp studies compared with the control experiment. This change was mainly accounted for by a decrease of VLDL triglyceride. The LDL cholesterol level fell by an average of 5% (p<0.05) during the high-insulin clamp and by 10% (p<0.05) during the hyperglycaemic clamp. The HDL cholesterol level did not change significantly. It is concluded that adipose tissue lipoprotein lipase activity in man is increased by physiological insulin levels during hyperglycaemia and also by supraphysiological insulin levels during euglycaemia, but is not influenced by physiological hyperinsulinaemia without hyperglycaemia. Low basal lipoprotein lipase activity is more sensitive to insulin-glucose stimulation than primarily high lipoprotein lipase activity. Acute hyperinsulinaemia decreases VLDL triglyceride and LDL cholesterol concentrations.     

Lipoprotein lipase in chronic lymphocytic leukemia: function and prognostic implications

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by the accumulation of a clonal population of B cells in peripheral blood, bone marrow, and lymphoid organs. More than 10 years ago, lipoprotein lipase (LPL) mRNA was identified as being strongly expressed in patients experiencing a more aggressive phenotype, while CLL patients with an indolent disease course lack expression of this marker. Since then, several reports confirmed the capability of LPL to predict CLL disease evolution at the moment of diagnosis. In contrast, data on the functional implications of LPL in CLL are scarce. LPL exerts a central role in overall lipid metabolism and transport, but plays additional, non‐catalytic roles as well. Which of those is more important in the pathogenesis of CLL remains largely unclear. Here, we review the current knowledge on the prognostic and biological relevance of LPL in CLL.     

Lipoprotein lipase gene variants and the effect of environmental factors on cardiovascular disease risk

Coronary heart disease (CHD) is a major cause of mortality in the Western world. CHD risk is known to be modified by both genetic and environmental factors. In this review, we look at the role of lipoprotein lipase (LPL) gene variants in predisposing to CHD risk and the important interaction between these genotypes and environmental factors (e.g. smoking). Gene–environmental interactions result in a greater than additive effect on risk and understanding these gene–environmental interactions has the potential not only for improving our understanding of the pathophysiology of the disease, but also in the development of new therapies and the targeting of specific therapies. For example, if a genotype increases risk in a particular environment, then those subjects would be encouraged to change their lifestyles more aggressively. Similarly at-risk subjects could be targeted with available therapies more appropriately.     

脂蛋白脂肪酶与胰岛素抵抗

脂蛋白脂肪酶(LPL)是脂蛋白代谢中甘油三酯分解的主要限速酶.LPL与胰岛素抵抗之间存在一定关系,可以通过多种途径导致胰岛素抵抗.据报道指出LPL可以作为胰岛素抵抗的一个生物指标.因此研究LPL对于改善胰岛素抵抗具有十分重要的意义.本文对LPL与胰岛素抵抗之间的关系作一简述.     

脂蛋白脂酶与代谢综合征

脂蛋白脂酶是脂质代谢的关键酶,主要水解甘油三酯,在乳糜微粒及极低密度脂蛋白的代谢中发挥重要作用.该酶的缺乏或活力异常,将导致糖、脂代谢紊乱.代谢综合征(MS)是以腹型肥胖,高血压,糖、脂代谢异常等多重心血管危险因素聚集为特征的临床综合征.越来越多的动物及临床证据表明,脂蛋白脂酶参与了 MS的发生、发展,故脂蛋白脂酶的研...     

Effects of Long-term Therapy with Labetalol on Lipoprotein Metabolism in Patients with Mild Hypertension

ABSTRACT. The effects of labetalol on serum lipoproteins, the intravenous fat tolerance test (IVFTT) and lipoprotein lipase (LPL) and hepatic lipase (HL) activities were studied in 16 patients with mild hypertension before and after 6 months of therapy. Most patients were found to be normotensive on 200 mg labetalol/day. Before therapy the mean concentration of serum TG was 0.75 ± 0.21 (SD) mmol/1, of total cholesterol 5.41 ± 1.25 mmol/1 and of HDL cholesterol 1.67 ± 0.61 mmol/1. After labetalol no significant changes were found in the concentrations of TG and cholesterol in the VLDL, LDL and HDL fractions. The mean values for the IVFTT and for LPL and HL activities were in the normal range and remained unchanged during therapy.     

脂蛋白脂肪酶与糖尿病

脂蛋白脂肪酶(LPL)是甘油三酯(TC)水解的限速酶,其基因缺失和基因多态性与糖、脂代谢紊乱的发生、发展密切相关.LPL功能紊乱可引起胰岛素抵抗甚至糖尿病,其可能机制包括:脂质异位沉积与胰岛素信号转导通路受损、内质网应激、氧化应激、炎性反应.明确LPL在糖尿病发生、发展中的作用,为防治糖尿病提供了新的思路.     

脂蛋白脂酶及其基因多态性与血管危险因素

脂蛋白脂酶（LPL）及其基因多态性已成为近年来研究的热点。LPL具有脂解作用和分子桥作用,其在不同位点的基因多态性（如HindⅢ、PvuⅡ、S447X、-93T→G、D9N、N291S、Gly188Glu、D8S261等）对血脂、血糖和血压水平等有一定的影响,与动脉粥样硬化和心脑血管病也存在一定的相关性。文章对LPL基因多态性与血管危险因素的关系进行了综述。     

脂蛋白脂酶基因Ser447→终止密码突变多态性与缺血性脑血管病的关系

目的:探讨中国人群中脂蛋白脂酶Ser447→终止密码突变(Ser447Stop)多态性与缺血性脑血管病(ICVD)的相关性。方法:共纳入ICVD患者112例(短暂性脑缺血发作36例,脑梗死76例)和对照者105例,用聚合酶链反应和限制性片段长度多态性分析确定其基因型。结果:ICVD组CG GG基因型频率显著低于对照组(0·161比0·391,OR=3·3,95%CI1·1~7·8,P=0·002)。ICVD亚组分析表明,短暂性脑缺血发作组CG GG基因型频率与对照组无显著差异,而脑梗死与对照组却有显著差异。结论:脂蛋白脂酶基因Ser447Stop多态性与ICVD特别是脑梗死呈显著相关性,可能是ICVD的一种保护性因素。     

脂蛋白脂酶与神经系统疾病

脂蛋白脂酶是脂质代谢和脂蛋白代谢过程的关键酶，在神经系统的多个区域均有表达，其中以海马最为丰富，其作用部位主要为毛细血管内皮细胞。神经系统的脂蛋白脂酶还可作为一种载体，向神经元转运胆固醇和维生素E，在维持神经元的正常功能中起重要作用。在神经系统病理状态下，脂蛋白脂酶的表达或活性都增高；某些伴有脂蛋白脂酶活性下降的疾病亦可导致神经病变。     

脂蛋白脂酶基因多态性与动脉粥样硬化

脂蛋白脂酶(lipoprotein lipase,LPL)是富含三酰甘油的脂蛋白的三酰甘油核心水解的限速酶,其不仅会影响脂蛋白水平,还在动脉粥样硬化的形成和发展中起着重要作用.LPL基因多态性会影响酶活性,从而具有促动脉粥样硬化或抗动脉粥样硬化的作用.文章对LPL基因多态性与动脉粥样硬化的关系进行了综述.     

LPL基因HindⅢ多态性与高脂血症和冠心病的关系

目的:探讨脂蛋白脂酶基因多态性与血脂水平、冠状动脉病变及其严重程度之间的关系。方法:采用PCR-RFLPs法,对西安地区208例行冠状动脉造影的患者,进行脂蛋白脂酶基因第8内含子区HindⅢ酶切位点多态性分析,依据显著病变（冠脉腔内狭窄率>50%）的冠脉支数确定冠状动脉病变严重程度。结果:脂蛋白脂酶基因HindⅢ多态性与血浆甘油三酯水平及高密度脂蛋白胆固醇水平密切相关（P<0.01）,与显著病变冠脉数相关（P<0.05）。结论:脂蛋白脂酶基因HindⅢ多态性与冠状动脉病变严重程度间存在相关性,可能与动脉粥样硬化进展的机制有关。     

Influence of apolipoprotein A-1 promoter polymorphism on lipid levels and responses to dietary change in Finnish adults

Objectives. To analyse the association between the G/A polymorphism in the apolipoprotein A-1 (apo A-1) promoter region and plasma lipid levels, as well as their responses to dietary change, in Finnish adults.
Subjects and design. Blood samples from 86 subjects (42 men, 44 women) who attended a dietary intervention study carried out in North Karelia in 1993 were available for the current analysis. The diet study consisted of a 2-week baseline period, followed by an 8-week intervention period, and an 8-week switchback period.
Intervention. Diet was modified to a low-fat, low-cholesterol diet during the dietary intervention.
Main outcome measures. Fasting plasma lipid, lipoprotein and apolipoprotein levels were determined.
Results. At baseline, the high-density lipoprotein (HDL) cholesterol and apo A-1 levels were higher ( P <0.01) and the triglyceride levels were lower ( P <0.05) in men, but not in women, with the A allele. The differences in HDL cholesterol and apo A-1 levels between genotypes remained during the low-fat, low-cholesterol diet and switchback periods. Apart from the difference between responses in apo A-1 during switchback to the original diet, lipid responses to dietary change did not differ significantly between genotypes.
Conclusion. Our findings indicate a significant association between the apo A-1 promoter polymorphism and plasma apo A-1 and HDL-cholesterol in men. In theory, the higher plasma HDL-cholesterol and apo A-1 levels in the GA/AA group may confer some protection against coronary artery disease. The differences in HDL-cholesterol and apo A-1 levels between genotypes persisted during different diets suggesting that the possible benefit is independent of fat and cholesterol intake.