Stimulating effect of intermediate-density lipoproteins (IDL) from hyperlipemic plasma on hepatic lipase

Summary The main lipoprotein density classes, namely very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), high-density lipoproteins₂ (HDL₂) and HDL₃ were investigated with respect to their influence on hepatic lipase (HTGL) activity in vitro.Lipoproteins from pooled normal plasma (NP) and from pooled hyperlipemic plasma (HP) were prepared by means of sequential ultracentrifugation. Hepatic lipase was determined radioenzymatically after preincubation with protamine sulfate. It could be demonstrated that IDL from HP were able to stimulate HTGL activity by approximately 100% above the baseline value. HDL₃ from both NP and HP revealed an inhibiting effect on HTGL activity. VLDL, LDL, and HDL₂ exhibited no significant effect on HTGL activity.It is speculated that HTGL could possibly represent a second pathophysiological pathway for the catabolism of IDL in hyperlipemia but this presumption is supported by only a few investigations in vivo.

---

Abbreviations HDL₂ High-density lipoproteins₂ - HDL₃ High-density lipoproteins₃ - HP Hyperlipemic plasma pool - HTGL Hepatic lipase - IDL Intermediate-density lipoproteins - LDL Low-density lipoproteins - NP Normal plasma pool - VLDL Very low-density lipoproteins     

Lipoproteins, post-heparin lipoprotein lipase and hepatic triglyceride lipase in patients with and without severe hyperlipemia caused by alcoholism

Because of the high incidence for development of a secondary hyperlipemia during chronic alcohol intake, this study was performed to look for a possible reason, why some patients produce severe hyperlipemia and other ones not. 15 male patients with chronic alcoholism (group I) who produce under influence of alcohol a secondary type-V hyperlipoproteinemia (type-V HLP) were compared with 15 male controls. Additionally, 8 male patients with chronic alcoholism (group II) who were normolipemic under alcohol abuse, and 7 male patients (group II) who had also produced type-V HLP under chronic alcohol abuse, but were teetotal since at least 6 months, were investigated. In comparison with controls, patients of group I showed significantly (p less than 0.01) increased plasma concentrations of very low-density lipoproteins (VLDL) and significantly decreased plasma concentrations of low-density lipoproteins (LDL), high-density lipoproteins2 (HDL2) and HDL3 (all p less than 0.01). Furthermore, the activities of postheparin lipoprotein lipase (LPL) and hepatic lipase (HTGL) were significantly decreased (both p less than 0.01). In patients of group III, the plasma concentrations of lipoproteins did not differ significantly from controls, but the activity of LPL was also significantly impaired (p less than 0.01), whereas the activity of HTGL was distinctly (p less than 0.01) increased. No significant difference between patients of group II and controls could be demonstrated. It is concluded that severe alcohol intake strongly impairs LPL in patients with chronic alcoholism. The pronounced increase of HTGL in patients of group III seems to protect these individuals from producing severe hyperlipemia under the influence of alcohol.     

茶多酚对实验性动脉粥样硬化兔脂蛋白脂酶、肝脂酶活性的影响及意义

目的:观察动脉粥样硬化(AS)发生发展过程中脂蛋白脂酶(LPL)、肝脂酶(HL)活性的变化及茶多酚(TP)的作用。方法:高脂食物AS模型兔口服茶多酚200μg·g^-1·d^-1,测定血浆中LPL、HL活性,同时用组织化学法检测动脉壁层组织中LPL活性、肝组织中HL活性。结果:AS组动脉粥样硬化病变血管壁与正常对照组血管壁组织中LPL活性差异无显著(P＞0.05);AS组肝组织中HL活性明显低于正常对照组(P＜0.05)。TP组肝组织中HL活性明显高于AS组(P＜0.05)、血浆中TC和LDL-c水平低于AS组(P＜0.05)、动脉粥样硬化斑块面积低于AS组(P＜0.05)。各组间血浆LPL、HL活性水平差异无显著(P＞0.05)。结论:茶多酚能增加实验性AS兔肝组织中HL脂酶活性,这一作用与降低血浆胆固醇水平和抗动脉粥样硬化密切相关。     

脂蛋白脂酶基因在子痫前期胎盘中的变化及意义

目的研究脂蛋白脂酶(lipoproteinlipase,LPL)mRNA在于痫前期患者胎盘组织中的表达与定位,探讨其在子痫前期病理生理过程中的作用。方法利用cDNA表达谱芯片检查子痫前期胎盘组织与正常胎盘组织之间的差异表达基因;根据筛选结果,采用半定量RT-PCR检测子痫前期患者胎盘组织(研究组)和正常孕妇胎盘组织(对照组)中LPLmRNA的表达;以原位杂交方法进行定位。结果在4轮杂交过程中,共筛选出22条有差异表达的基因,其中LPL基因为表达降低基因之一;正常胎盘组织和子痫前期胎盘组织中均存在LPLmRNA,子痫前期胎盘组织中LPLmRNA表达明显低于正常胎盘组织(0.208±0.067vs0.524±0.139,P<0.05);LPLmRNA分布在胎盘绒毛滋养细胞胞浆。结论胎盘组织中LPL的低表达可能参与子痫前期的发病过程。     

Lipoprotein lipase activity in patients with combined hyperlipidaemia

The aetiology of familial combined hyperlipidaemia remains obscure, with both genetic and environmental factors contributing to the phenotype, which is frequently associated with premature coronary heart disease. We have studied lipoprotein lipase (LPL) activity and hepatic lipase (HL) activity in patients with coronary heart disease to determine whether variation in lipase activities contributes to this phenotype. Forty-one patients (mean age 50 years; 30 male) were selected on the basis of cholesterol levels above 6.5 mmol/l and triglyceride levels above 2.2 mmol/1, with apoprotein B values over the 90th percentile. There was a family history of premature coronary heart disease in 78% and a personal history in 64%, at mean age 44, the patient group therefore predominantly corresponded to the common definition of familial combined hyperlipidaemia, appropriate in the absence of molecular markers. None of the patients was diabetic; hypertension and smoking were not over represented. Blood samples were taken following intravenous administration of heparin (100IU/kg body wt), and LPL and HL activities were measured. Mean post-heparin LPL was significantly lower in patients than controls 10 min after heparin administration (2.98 ± 1.04 and 3.86 ± 0.93 mol ml^-1 h^-1, respectively, P = 0.001), and 37% patients had values below the 10th percentile of controls. Both male and female patients had significantly higher HL activities than their respective controls at 5, 10, 20 and 30 minutes postheparin. As expected, both female patients and controls had lower HL activities than males, although this sex difference did not reach statistical significance in the patient group. Mean lipid and lipoprotein results were: cholesterol 8.2 mmol/1; triglycerides 4.2 mmol/l; high-density lipoprotein cholesterol 0.90 mmol/1; apoprotein Al 122 mg/dl; apoprotein B 171 mg/dl; lipoprotein (a) 23 mg/dl (median 10 mg/dl). High-density lipoprotein cholesterol and triglycerides were negatively correlated (r = -0.26, P = 0.05). HL was significantly related to body mass index at all time points whereas the negative correlation between post-heparin LPL and body mass index was significant only 30 min after heparin administration. Post-heparin LPL was only weakly correlated with triglycerides 10 and 20 min after heparin administration. These lipid and lipoprotein results are clearly potentially atherogenic as indicated by the extent of premature coronary heart disease in the group described. A decrease in LPL activity may contribute to this pattern.Abbreviations FCHL familial combined hyperlipidaemia - CHD coronary heart disease - LPL lipoprotein lipase - HL hepatic lipase - HDL high-density lipoprotein - VLDL very low density lipoprotein; - apo apoprotein - TG triglyceride - BMI body mass index Correspondence to: M. Seed     

家族性脂蛋白脂酶缺乏症的基因分析

目的分析中国家族性脂蛋白脂酶（ｌｉｐｏｐｒｏｔｅｉｎｌｉｐａｓｅ,ＬＰＬ）缺乏症的基因突变。方法以基因组ＤＮＡ为模板,借助聚合酶链反应扩增产物,用双脱氧末端终止法,对患者ＬＰＬ的ＤＮＡ序列进行检测。结果对ＬＰＬ基因的９个外显子测序,发现在第６外显子中一碱基发生错义突变,即６Ｇ９７９→Ａ（Ｇｌｕ２４２→Ｌｙｓ）,这是一杂合子的等位基因突变。结论ＬＰＬ基因在该位置的突变可能是导致患者ＬＰＬ活性显著降低和血清甘油三酯增高的原因。该位点的基因突变系首次报道。同时也为研究动脉粥样硬化和高脂血症等多种代谢疾病的发病机理提供了重要证据。     

Atypical type III hyperlipoproteinemia in a patient with Ig A myelomatosis

Summary We studied a 58-year-old woman with severe therapy-refractory hyperlipidemia, xanthomatosis, and multiple myeloma (immunoglobulin A, lambda light chain). The lipid disorder became evident about half a year prior to the expression of myelomatosis. Clinical symptoms were similar to those found in classical type III hyperlipoproteinemia but the underlying metabolic defect was different from the one described in this primary dyslipoproteinemia. The patient has the heterozygous apolipoprotein E3/2 phenotype and her VLDL-cholesterol/serum-triglyceride ratio is unusually low at 0.05. Evidence is given that the hyperlipoproteinemia is due to an impaired catabolism of intermediate density lipoproteins probably because of a reduced hepatic triglyceride lipase activity.Abbreviations AIH autoimmune hyperlipidemia - Chol cholesterol - HDL high density lipoproteins - HLP hyperlipoproteinemia - HTGL hepatic triglyceride lipase - IDL intermediate density lipoproteins - IEF isoelectric focusing - Ig immunoglobulin - LDL low density lipoproteins - LPL lipoprotein lipase - PL phospholipids - TG triglycerides - VLDL very low density lipoproteins     

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.     

重度子痫前期孕妇血清脂蛋白脂酶与血脂相关性的研究（附910例临床资料）

目的探讨脂蛋白脂酶（LPL）在子痫前期血脂代谢中的临床意义。方法回顾性分析310例重度子痫前期孕妇（子痫前期组）和300例健康晚孕妇女（晚孕组）、300例健康未孕育龄妇女（未孕组）的血脂代谢情况;检测26例子痫前期组、30例晚孕组和30例未孕组血IJPL、TG、HDL浓度。结果子痫前期组存在显著的高TG、低HDL血脂代谢异常,LPL与TG呈负相关、与HDL呈正相关。结论子痫前期存在显著的高血脂异常代谢,LPL可能通过参与异常血脂代谢而导致子痫前期发病。     

Adipose tissue lipoprotein lipase activity in rats maintained at a reduced body weight

Male rats fed a cellulose-diluted diet maintained a reduced body weight. Adipose tissue lipoprotein lipase (LPL) activity decreased after two days of cellulose feeding, but was not different from chow-fed control levels with weight stabilized at 90% or 70% of the control group. Plasma triglyceride concentration decreased with weight loss and remained depressed with stabilized reduced weight. Regaining lost weight had no effect on LPL activity when compared with chow-fed controls or with levels obtained for the weight-reduced group. However, plasma triglyceride concentration returned to chow-fed control levels with weight gain. The disparity between these results and those obtained in obese human beings lends support to the hypothesis that the increase in adipose tissue LPL activity in weight-reduced obese human beings is indicative of a defect in regulation of adipose tissue metabolism.     

Fenofibrate improves postprandial chylomicron clearance in II B hyperlipoproteinemia

In 11 patients with 1113 hyperlipoproteinemia we studied fasting lipids, lipoproteins, lipoprotein-modifying enzymes, and postprandial lipid metabolism after a standardized oral fat load supplemented with vitamin A before and 12 weeks after treatment with fenofibrate, a third-generation fibric acid derivative. Fasting plasma cholesterol, triglycerides, low-density lipoprotein cholesterol decreased significantly (P < 0.05, P < 0.01, P < 0.01), high-density lipoprotein subfraction 3 cholesterol increased significantly (P < 0.05), and high-density lipoprotein subfraction 2 cholesterol remained unchanged. Postprandial lipemia, i.e., the integrated postprandial triglyceride concentrations corrected for the fasting triglyceride level, and postprandial chylomicron concentrations, as assessed by biosynthetic labeling of chylomicrons with retinyl palmitate, decreased by 40.6% and 60.1% (P < 0.05; P < 0.05), respectively. The activity of lipoprotein lipase (LPL) increased by 33.6% (P < 0.05); the increase in LPL during fenofibrate treatment was positively correlated with the increase in high-density lipoprotein cholesterol (r = 0.84; P < 0.005). Hepatic lipase and cholesteryl ester transfer protein mass and activity remained unchanged. We conclude that lipid-lowering therapy with fenofibrate ameliorates fasting and, more profoundly, postprandial lipoprotein transport in hypertriglyceridemia by curbing postprandial triglyceride and chylomicron accumulation, at least in part, through an increase in LPL activity.Abbreviations LDL low-density lipoproteins - HDL high-density lipoproteins - LPL lipoprotein lipase - HL hepatic lipase - CETP cholesteryl ester transfer protein - CHD coronary heart disease - VLDL very low density lipoproteins - TG triglycerides - apo apolipoprotein Correspondence to: J.R. Patsch     

Lipoprotein lipase in non-small cell lung cancer tissue is highly expressed in a subpopulation of tumor-associated macrophages

High lipoprotein lipase (LPL) activity in non-small cell lung cancer (NSCLC) tissue strongly predicts shorter patient survival. We tested the hypothesis that in NSCLC tissue, macrophages are the major site of LPL expression. LPL expression in the entire NSCLC tissue and in the adjacent non-cancer lung tissue was compared to the expression of genes preferentially expressed in macrophages. LPL expression at the cellular level was analyzed by mRNA fluorescence in situ hybridization. In the whole cancer tissue (but not in the adjacent non-cancer tissue), expression of LPL correlated with expression of genes preferentially expressed in macrophages (MSR1, CD163, FOLR2), but not with expression of genes preferentially expressed in tumor cells. All cells in the cancer and adjacent non-cancer tissue exhibit low LPL expression. However, in cancer tissue only, there were individual highly LPL-expressing cells which were macrophages. These LPL-overexpressing cells were approximately 10 times less abundant than anti-CD163-stained, tumor-associated macrophages. To conclude, in NSCLC tissue, a subpopulation of tumor-associated macrophages highly expresses LPL. Because tumor-associated macrophages are pro-tumorigenic, these cells should be further characterized to better understand the underlying nature of the close relationship between high LPL activity in NSCLC tissue and shorter patient survival.     

新LPL基因复合杂合变异导致的一例新生儿脂蛋白脂肪酶缺乏症

目的明确1例脂蛋白脂肪酶缺乏症新生儿的遗传学病因。方法应用目标区域捕获测序技术对患儿进行遗传代谢疾病相关基因检测,并对可疑变异位点在患儿及其父母进行Sanger测序验证。结果基因检测结果显示患儿LPL基因存在c.347G>C(p.Argll6Pro)和c.472T>G(p.Tyrl58Asp)复合杂合变异,父亲携带c.347G〉C(p・Argll6Pro)杂合变异,母亲携带c.472T>G(p.Tyrl58Asp)杂合变异,因此患儿的变异分别来源于其父母。结论LPL基因c.347G>C(p.Argll6Pro)和c.472T>G(p.Tyrl58Asp)复合杂合变异可能是这例脂蛋白脂肪酶缺乏症新生儿的致病原因。     

Effects of a brisk walk on lipoprotein lipase activity and plasma triglyceride concentrations in the fasted and postprandial states

This study aimed to determine whether changes in plasma heparin-releasable lipoprotein lipase (LPL) activity following a brisk walk were associated with decreases in fasting and/or postprandial triglyceride (TG) concentrations. Two groups of pre-menopausal women participated. In one group (fasting study group, n=10), TG concentrations and post-heparin plasma LPL activity were measured in the fasted state on two occasions: ~18 h after a 2-h treadmill walk at 50% maximal oxygen uptake (exercise trial); and after a day of no exercise (control trial). The other group (postprandial study group, n=9) undertook two oral fat tolerance tests (blood samples taken fasting and for 6 h after a high-fat meal), with plasma LPL activity measured 6 h after meal ingestion. Pre-conditions were the same as for the fasting study group (i.e. control and prior exercise). Prior exercise reduced fasting TG concentrations by 23 (7)% (fasting study group) [mean (SEM)] and by 18 (9)% (postprandial study group) (both P<0.05), and the postprandial TG response by 23 (6)% (postprandial study group) (P<0.01). Plasma LPL activity was not significantly increased by exercise in either the fasting or postprandial study groups. However, exercise-induced changes in both fasting and postprandial LPL activity were significantly correlated with the respective exercise-induced changes in fasting TG concentration and the postprandial TG response (r=−0.70 and −0.77 respectively, P<0.05 for both). These data suggest that increased LPL activity may contribute to the hypotriglyceridaemic effect of moderate exercise, although other mechanisms are also likely to be involved. Electronic Publication     

Adipose tissue lipoprotein lipase activity in rats with obesity-inducing hypothalamic knife cuts

Three experiments examined the effects of obesity-inducing parasagittal hypothalamic knife cuts on adipose tissue lipoprotein lipase (LPL) activity in female rats. Knife cuts induced a 4-fold increase in adipose tissue LPL activity. Knife-cut rats with controlled insulin levels were hyperphagic but showed no increase in adipose tissue LPL activity or body weight gain. Prevention of the hyperphagia by food restriction also blocked the changes in LPL activity and weight gain. Finally, exogenous insulin treatment increased adipose tissue LPL activity in the absence of hyperphagia in neurologically-intact rats. We conclude that increased adipose tissue LPL activity may play a permissive role in the development of hypothalamic obesity, with the increase in enzyme activity being secondary to knife-cut-induced hyperinsulinemia.     

Dependence on Ca2+ of lipoprotein lipase stability

Macrophages continuously secrete lipoprotein lipase (LPL) into the culture medium. When LPL was collected from thioglycollate-elicited peritoneal macrophages (Tg-M?) or J774.1 cells over a 4 h period in Ca2+ and Mg2(+)-free Dulbecco's modified Eagle's medium (d-DMEM) the activity in the collection medium was reduced by 40-62% and 23%, respectively, as compared to that expressed in full medium (DMEM). Ca2+ supplementation during the collection period in d-DMEM augmented LPL activity in the medium; about 1 mM Ca2+ was required for attainment of activity comparable to that expressed in DMEM. Addition of Ca2+ during the assay did not enhance LPL activity collected into d-DMEM. Addition of EGTA to the assay mixture reduced LPL activity by 34-60% and when present in the collection medium, EGTA led to a reduction in enzyme activity greater than 90%. A 4 h incubation of Tg-M? in 3 mM EGTA led to an almost complete loss of intracellular Ca2+ (measured by efflux of 45Ca2+ from preloaded cells), yet there was no change in the overall synthesis and secretion of proteins and in the phagocytic capability of the cells. LPL activity in the enzyme collection medium after its removal from cell monolayers was stable at least up to 4 h at 0 degrees C and at 23 degrees C. Activity was progressively lost with increased temperatures: up to 40% loss at 37 degrees C in 4 h. Addition of EGTA to the above medium led to an enhanced rate of irreversible enzyme inactivation: 76-86% loss of activity in 4 h at 37 degrees C. No inactivation was observed at 0 degrees C and at 23 degrees C in the presence of EGTA. The results indicate a critical role for Ca2+ in enzyme stabilization.     

Dietary effects on glycogen and lipoprotein lipase activity in skeletal muscle in man

The influence of short-term adaptation to a fat and protein enriched diet (F+P) and a carbohydrate enriched diet (CHO) on skeletal muscle lipoprotein lipase (LPL) activity and muscle glycogen levels was evaluated in 7 males. Muscle biopsies were taken from the m. vastus lateralis after an uncontrolled, mixed diet (M), after a 3 day F+P diet preceded by intense exercise, and after a 3 day CHO diet. After the F+P diet glycogen concentration was 55% that of the M diet while LPL activity increased by 21% (n. s.). After the CHO diet glycogen levels increased by 82% and LPL activity decreased by 55% compared to the M diet (p<0.01). The changes in LPL after the CHO diet were related to the changes in glycogen concentration (r = 0.98, p<0.01). LPL activity in the control situation was directly related to percent slow twitch (ST) muscle fibre type (r = 0.95, p<0.01). The results suggest that the uptake of fat from the circulation may be actively regulated by the muscle as a function of intramuscular substrate availability and that this regulation may be related to muscle fibre type composition.     

Ovarian modulation of lipoprotein lipase activity in white adipose tissue of ground squirrels

Golden-mantled ground squirrels were ovariectomized (OVX) or Sham-OVX during the weight gain phase of the circannual body weight cycle. Other squirrels, OVX or Sham-OVX during the weight loss phase, were subcutaneously implanted with estradiol-filled or empty Silastic capsules. The mass of several fat pads as well as adipose tissue lipoprotein lipase (LPL) activity were determined at autopsy. Ovariectomy at either phase of the annual cycle was without effect on body weight. However, LPL activity of the parametrial fat pad was increased in OVX as compared to Sham-OVX squirrels. Fourteen days of estradiol treatment during the weight loss phase decreased the mass and LPL activity of the retroperitoneal fat depot but did not affect these parameters in perirenal adipose tissue. Although estradiol exerts different or opposite effects on body mass and food intake of rats and ground squirrels, ovariectomy and estrogen treatment affect LPL activity in a similar fashion in both species.     

Exercise-induced changes in lipoprotein lipase activity (LPLA) in skeletal muscles of the dog

The aim of this work was to study the effect of physical exercise on muscle lipoprotein lipase activity (LPL) in dogs. Existence of two forms of LPL: heparin releasable and unreleasable was demonstrated in skeletal muscles, and the changes in the activity of both forms were followed during 3 h treadmill running, using biopsy samples taken from m. biceps femoris.During the first two hours of exercie the heparin releasable form of LPL was progressively increasing, whereas the heparin unreleasable form of the enzyme was decreasing. Thus, a significant negative correlation between activities of the two forms was ascertained (r=0.72,P<0.01). In the final period of exercise, activity of the heparin releasable form of LPL tended to stabilize on the enhanced level, and activity of the heparin unreleasable form increased.In the further series of experiments a relationship between exercise intensity and activity of the heparin releasable form of LPL was studied during 1 h exercise bouts.A significant positive correlation (r=0.84,P<0.001) was ascertained between LPL activity and intensity of work. A comparison between LPL activity in the muscle engaged in exercise (m. biceps femoris) and nonactive muscle (m. coccygeus) revealed that the enhancement of the enzyme activity during physical work does not occur in the latter.In conclusion: it was found that physical exercise induces a marked intensity-dependent increase of LPL activity in working muscles, which is probably caused by an elevated transport of the enzyme molecules from the muscle cells to the intravascular space. The latter suggestion is based on the reciprocal changes of the heparin releasable and unreleasable (probably intracellular) forms of LPL.This work was supported by the Polish Academy of Sciences within the project 10.4.     

Recurrent missense mutations at the first and second base of codon Arg243 in human lipoprotein lipase in patients of different ancestries

Mutations in the lipoprotein lipase (LPL) gene are the most common cause of familial chylomicronemia. Here we define the molecular basis of LPL deficiency in four patients of German, French, Dutch, and Chinese descent. We show that two of the probands of Dutch and Chinese origin have a previously described Arg²⁴³His mutation while the patients of German and French descent have a novel Arg²⁴³ Cys substitution in their LPL gene. Haplotype analysis is in favour of two separate origins for the Arg²⁴³ Cys substitution which together with the Arg²⁴³ His mutation would implicate three recurrent mutations involving the first and second nuclcotides of the codon encoding Arg²⁴³ of the LPL gene. The recurrent mutations affecting the first and second nucleotide of CGC coding for the normal Arg residue are support for the high mutability of CpG dinucleotides within the LPL gene. © 1994 Wiley-Liss, Inc.