Inheritance of apolipoprotein C-II deficiency with hypertriglyceridemia and pancreatitis.

A study of the relatives of a patient with apolipoprotein C-II deficiency showed that the defect is inherited as an autosomal recessive trait. The kindred studied originated from an isolated population in which considerable inbreeding has occurred for 140 years. Seven homozygotes had marked fasting chylomicronemia and triglyceridemia, and lacked detectable apolipoprotein C-II by several assay methods. Five homozygotes had experienced one to many attacks of pancreatitis from as early as six years of age. Obligate heterozygotes had apolipoprotein C-II concentrations about 30 to 50 per cent of normal values and had normal plasma triglyceride concentrations. This metabolic defect should be considered in patients with markedly elevated plasma triglycerides who have apparent lipoprotein lipase deficiency, and usually also have pancreatitis.     

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     

A case of apolipoprotein C-II deficiency with coronary artery disease

A 56-year-old male with apolipoprotein C-II deficiency experienced a myocardial infarction without pancreatitis. A coronary angigram showed complete occlusions of both the right and circumflex coronary arteries. His serum lipid levels were as follows: fasting total cholesterol 3.15 mmol/l; postprandial total cholesterol 3.62 mmol/l; fasting triglycerides 1.46 mmol/l; postprandial triglycerides 6.14 mmol/l; fasting high-density lipoprotein-cholesterol 0.47 mmol/l; and postprandial high-density lipoprotein cholesterol 0.36 mmol/l. His fasting level of plasma apolipoprotein C-II was 0.0005 g/l, but his plasma levels of other apolipoproteins were within normal ranges. A DNA sequence analysis of the apolipoprotein C-II gene showed no mutations in exon 1, 2, 3, or 4, where most gene mutations related to apolipoprotein C-II deficiency occur. We report this patient's very rare heterozygous apolipoprotein C-II deficiency with coronary artery disease. Although this patient had some risk factors for coronary artery disease, coronary atherosclerosis in this patient might have occurred as a result of lipoprotein abnormalities caused by at least one mutation in the apolipoprotein C-II gene. Received: 7 May 2001 / Accepted: 30 January 2002     

The effect of the apolipoprotein E polymorphism on lipid levels in patients with familial defective apolipoprotein B-100

Summary Serum lipid concentrations of patients with familial defective apolipoprotein B-100 (FDB) show a high interindividual variability although the underlying defect is caused by a single point mutation. On the other hand, several genetic factors modulating serum cholesterol levels are known, such as DNA polymorphisms of the apopolipoprotein B or the apolipoprotein E (apo E) gene. To assess the effect of the apo E polymorphism on serum cholesterol, lipid levels of FDB patients (n=36) were compared with those of a normolipidemic control group (n=272) according to their apo E genotype. For the FDB group mean values of low-density lipoprotein (LDL) cholesterol (mg/dl) were 225.7 ± 53.7 for E3/2 genotype (n = 3), 234.2±48.3 for E3/3 genotype (n=20), and 252.4±73.8 for E4/3 genotype (n=13). Means of triglycerides (mg/dl) were 121.0±21.2, 114.8± 60.7, and 110.0 ± 62.8 for the respective apo E genotypes. The calculated average effect of the apo E alleles on LDL cholesterol levels was –6.0% for allele e2 and +3.7% for e4 relative to the whole FDB group. The effect on triglyceride levels was +7.5% for e2 and –3.6% for e4. The control group showed a similar variation in LDL cholesterol depending on the different apo E genotypes. About 6% of the total variation in LDL cholesterol can be accounted for by the apo E locus in normolipidemic and hypercholesterolemic individuals alike.Abbreviations FDB familial defective apolipoprotein B-100 - apo apolipoprotein - LDL low-density lipoprotein - VLDL very low density lipoprotein - HDL high-density lipoprotein - PCR polymerase chain reaction Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

Very low density lipoprotein apolipoprotein B metabolism in humans

Summary The human plasma lipoproteins encompass a broad spectrum of particles of widely varying physical and chemical properties whose metabolism is directed by their protein components. Apolipoprotein B₁₀₀ (apo B₁₀₀) is the major structural protein resident in particles within the Svedberg flotation range 0–400. The largest of these, the very low density lipoprotein (VLDL), rich in triglyceride, are metabolised by sequential delipidation through a transient intermediate density lipoprotein (IDL) to cholesterol-rich low density lipoproteins (LDL). Several components contribute to the regulation of this process, including (a) the lipolytic enzymes lipoprotein lipase and hepatic lipase (b), apolipoproteins B, CII, CIII and E, and (c) the apolipoprotein B/E or LDL receptor. Lipoprotein lipase acts primarily on large VLDL of Sf 60–400. Hepatic lipase on the other hand seems to be critical for the conversion of smaller particles (Sf 12–60) to LDL (Sf 0–12). Although most apo B₁₀₀ flux is directed to the production of the delipidation end product LDL, along the length of the cascade there is potential for direct removal of particles from the system, probably via the actions of cell membrane receptors. This alternative pathway is particularly evident in hypertriglyceridaemic subjects, in whom the delipidation process is retarded.VLDL metabolism shows inter subject variability even in normal individuals. In this regard, apolipoprotein E plays an important role. Normolipidaemic individuals homozygous for the apo E₂ variant exhibit gross disturbances in the transit of B protein through the VLDL-IDL-LDL chain.Abbreviations apo B, C, E Apolipoprotein B, C, E - CETP Cholesteryl ester transfer protein - FCH Familial combined hyperlipidaemia - FH Familial hypercholesterolaemia - FHTG Familial hypertriglyceridaemia - HDL High density lipoprotein - HL Hepatic lipase - IDL Intermediate density lipoprotein - LDL Low density lipoprotein - LpL Lipoprotein lipase - RFLP Restriction fragment length polymorphism - Sf Svedberg flotation coefficient - VLDL Very low density lipoprotein - WHHL Watanabe heritable hyperlipidemic     

Effects of short-term melatonin administration on lipoprotein metabolism in normolipidemic postmenopausal women

OBJECTIVE: To investigate the effects of short-term administration of melatonin on lipoprotein metabolism in normolipidemic postmenopausal women. METHODS: Fifteen such women received 6.0 mg melatonin daily for 2 weeks. Blood was sampled before and after treatment. We measured concentrations of total cholesterol and total triglyceride in the plasma, as well as the levels of cholesterol, triglyceride, and protein in the very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Plasma apolipoprotein levels were determined by immunoturbidimetric assay. Activities of lipoprotein lipase, hepatic triglyceride lipase, and lecithin cholesterol acyltransferase were also determined by enzymatic analysis. RESULTS: Melatonin administration significantly increased the plasma levels of triglyceride by 27.2% (P < 0.05), of VLDL-cholesterol by 37.2% (P < 0.01), of VLDL-triglyceride by 62.2% (P < 0.001), and of VLDL-protein by 30.0% (P < 0.05). However, the plasma total cholesterol level and the concentration of lipid and protein in LDL and HDL were not significantly affected. Melatonin significantly increased the plasma levels of apolipoprotein C-II by 29.5% (P < 0.005), of C-III by 17.1% (P < 0.001), and of E by 7.6% (P < 0.05). The plasma levels of apolipoprotein A-I, A-II, and B were not altered. Melatonin significantly inhibited the activity of lipoprotein lipase by -14.1% (P < 0.05), but did not significantly affect the activities of hepatic triglyceride lipase or of lecithin cholesterol acyltransferase. CONCLUSIONS: Findings indicate that melatonin increases the plasma level of VLDL particles by inhibiting the activity of lipoprotein lipase, but may not affect the plasma levels of LDL and HDL particles in postmenopausal women with normolipidemia.     

Deficiency of hepatic lipase activity in post-heparin plasma in familial hyper-alpha-triglyceridemia

Hyper-alpha-triglyceridemia is a rare dyslipoproteinemia characterized by a pronounced increase in the concentration of triglycerides in the plasma high density lipoprotein (HDL) fraction. One case with this condition, an apparently healthy 61-year-old man, has been studied. Additional lipoprotein abnormalities were present, such as abnormally cholesterol-rich very low density lipoproteins (VLDL) with retarded electrophoretic mobility (beta-VLDL) and triglyceride enrichment of low density lipoproteins (LDL). The patient's plasma concentration of apolipoproteins A-I, A-II and B were normal and those of C-I, C-II, C-III and E were elevated. No abnormal forms of the soluble apolipoproteins of VLDL and high density lipoproteins (HDL) were found after analysis by isoelectric focusing. Lecithin:cholesterol acyltransferase activities, plasma cholesterol esterification rates and lipid transfer protein activities were normal. Post-heparin plasma activity of hepatic lipase was virtually absent and that of lipoprotein lipase was reduced by 50%. In plasma of this patient, HDL was almost exclusively present as large triglyceride-rich particles corresponding in size to particles of the HDL2 density fraction. The only brother of the patient also had hyper-alpha-triglyceridemia together with the other lipoprotein abnormalities described for the index case and deficiency of postheparin plasma activity of hepatic lipase. The findings presented below support the hypothesis that one primary function of hepatic lipase is associated with degradation of plasma HDL2. Deficiency of this enzyme activity thus causes accumulation of HDL2 in plasma leading to hyper-alpha-triglyceridemia. The results further suggest that the abnormal chemical and electrophoretic properties of VLDL and LDL in plasma from the patient, reminiscent of type III hyperlipoproteinemia, are secondary to the lack of the action of hepatic lipase on the HDL particles.     

Selective deficiency of hepatic triglyceride lipase in uremic patients.

To investigate the pathogenesis of hypertriglyceridemia in patients with renal disease we measured plasma lipoprotein composition as well as hepatic triglyceride lipase and lipoprotein lipase in post-heparin plasma. Three groups with renal disease were studied: conservatively treated chronic uremia; patients undergoing maintenance hemodialysis; and renal-allograft recipients. A selective decrease of hepatic triglyceride lipase with normal lipoprotein lipase was found in conservatively treated uremia and in patients undergoing hemodialysis. Elevated levels of very-low-density lipoproteins and increased triglycerides in low-density lipoproteins occurred in these patients. In contrast, hepatic triglyceride lipase and lipoprotein lipase were both normal in patients after renal transplantation who had Type II hyperlipoproteinemia as a common lipoprotein pattern with increased low-density-lipoprotein cholesterol and decreased high-density-lipoprotein cholesterol concentrations. The accumulation of a triglyceride-rich low-density lipoprotein in the majority of patients with renal disease may be the consequence of low hepatic triglyceride lipase.     

Genetic polymorphisms of the apolipoprotein A-IV in a Greek population and their relation to plasma lipid and lipoprotein levels

Apolipoprotein (apo) A-IV is a protein component of triglyceride-rich lipoproteins and high-density lipoproteins (HDL). In this study, two common genetic polymorphisms of the apoA-IV gene [codons 347(allele A and T) and 360 (allele 1 and 2)] were investigated in Greek patients with hyperlipidaemia and in healthy individuals matched for age, sex and smoking habits. In both study populations we evaluated the effect of these polymorphic sites on lipid and lipoprotein plasma levels and the body mass index (BMI). The frequencies of the 1/1 and 1/2 genotypes in codon 360 were 0.94 and 0.06 in hyperlipidemic patients and 0.92 and 0.08 in the control population, respectively. The frequencies of the A/A, A/T and T/T genotypes in codon 347 were 0.62, 0.34 and 0.04 in hyperlipidemic patients and 0.59, 0.33 and 0.08 in the control population, respectively. None of the above genotype frequency differences between the study populations reached statistical significance. The control population was not affected by any polymorphism of the apo A-IV gene. Hyperlipidaemic patients, carriers of the allele 2 (1/2 genotype), had significantly lower plasma triglyceride levels than carriers of the allele 1 (p = 0.03). Genetic variation in codon 347 had no influence on lipid and lipoprotein plasma levels. None of the polymorphisms at codons 360 and 347 affected the BMI. In conclusion, this study describes for the first time the genotype frequencies for polymorphic sites in codons 360 and 347 of the apo A-IV gene in a Greek population and suggests that the presence of the allele 2 is associated with lower plasma triglyceride levels in hyperlipidaemic patients.     

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     

A novel apolipoprotein E5 variant with a 24-bp insertion causing hyperlipidemia

A tandem 24-bp insertion in the apolipoprotein E (apo E) gene was detected in a patient with elevated triglyceride, apolipoprotein (apo) CII, and apo CIII levels. This novel variant, apo E5ss, showed in position apo E5 by isoelectric focusing and was of larger molecular weight than apo E3 during two-dimensional gel electrophoresis. Polymerase chain reaction-single strand conformation polymorphism analysis using the primer pairs that cover all the coding regions was useful for rapid detection of the variant of the apo E allele. Apo E5ss may have a 24-bp insertion caused by slipped mispairing, resulting in a tandem duplication of amino acid residues 135–142 [APOE, 24-BP INS, DUP CODONS 135–142]. The proband was the only person with apo E5ss among the 806 Japanese males that we examined. We inspected six other reported apo E5 variants in the literature. Received: July 10, 2001 / Accepted: August 8, 2001     

Serum lipid and apolipoprotein levels in patients with chronic pancreatitis]

Serum lipid and apolipoprotein (apo A-I, A-II, A-IV, B, C-II, C-III, E and H) levels were determined in 26 patients with chronic pancreatitis without complications such as liver disease or diabetes mellitus. These patients were divided into two groups, CP-I (n = 16) and CP-II (n = 10), according to the clinical criteria for chronic pancreatitis. HDL-cholesterol and apo A-I levels in CP-I and CP-II groups significantly decreased compared to those in sex- and age-matched healthy controls (p less than 0.05), whereas there were not significant differences in triglyceride and total cholesterol levels between these groups and controls. On the other hand, apo A-IV levels in CP-I and CP-II were 7.1 +/- 1.0 mg/dl and 8.3 +/- 1.5 mg/dl, respectively and these values were significantly lower than 11.2 +/- 1.8 mg/dl in controls (p less than 0.001). In this study, the serum lipids apparently showed normal levels in patients with chronic pancreatitis who had no severe complication, and the markedly low apo A-IV levels in these patients were considered to be mainly due to the decrease of lipid absorption from the intestine.     

Antibodies of predetermined specificity to apolipoprotein C-II elicited with a synthetic peptide. Characterization and use for immunoassays

Antibodies of predetermined specificity raised against a synthetic peptide corresponding to the C-terminal region of apolipoprotein C-II (Apo C-II) 63-79 were shown to be specific for the apolipoprotein by Western blot. The recognition by these antibodies of Apo C-II containing lipoprotein particles (both isolated and in plasma) was studied in a fluid-phase radioimmunoassay and the affinity constant for plasma was determined. The role of lipids in the expression of epitopes was studied by comparing the antigenicity of intact and delipidated Apo C-II containing fractions. The antibodies proved to be as suitable as conventional anti-protein antibodies in an immunoenzymometric assay and, moreover, were able to develop 'rockets' in an electroimmunoassay.     

Population frequency of apolipoprotein E5 (Glu3→Lys) and E7 (Glu244→Lys, Glu245→Lys) variants in western Japana

Apolipoprotein (apo) E modulates the catabolism of chylomicrons and of very low density lipoprotein remnants. It has three major isoforms (apo E2, E3, E4) and some rare variants. To detect the variants of apo E, blood specimens from 1269 Japanese subjects were analyzed using isoelectric focusing with immunoblotting. The E5 and E7 variants were identified by IEF in 2 and 18 subjects, respectively. Both E5 (Glu3→Lys) carriers were confirmed by PCR-mediated site-directed mutagenesis, and all E7 (Glu244→Lys, Glu245→Lys) carriers were confirmed by the amplification refractory mutation system. The relative frequencies of the ε5 and ε7 alleles were 0.001 and 0.007, respectively. High concentrations of total cholesterol (>220 mg/dl) were detected in five of the subjects expressing apo E7 and one subject expressing apo E5, and eight subjects heterozygous for apo E7 showed elevated plasma triglyceride concentrations (>150 mg/dl). In 621 healthy subjects, the mean triglyceride concentration in subjects with apo E7/3 appeared to be higher than in those with apo E3/3, but the difference was not statistically significant.     

Molecular cloning and characteristics of a new apolipoprotein C-II mutant identified in three unrelated individuals with hypercholesterolemia and hypertriglyceridemia

A new rare mutant form of apolipoprotein C-II (apoC-II), designatedapoC-II_SF, was identified in three unrelated hyperlipidemicpatients. The first was a Caucasian male with a total cholesterol(TC) of 313 mg/dl and total triglyceride (TG) of 282 mg/dl,the second an African-American female (TC 345 mg/dl, TG 203mg/dl) and the third, an African—American male (TC 345mg/dl, TG 1000 mg/dl). Each subject was found to be heterozygousfor a G to A substitution in the codon for residue 38, resultingin a Lys for Glu exchange. This accounts for the increased plvalue of 5.3. The third patient, in addition to apoC-II_SF, hadapoC-II₂, another charge variant. This was determined by DNAsequencing, confirming the Gln for Lys change at residue 55previously predicted by analysis of peptide fragments in thislaboratory. Similar Michaelis constants of activation and activationenergies were observed when the ability of apoC-II_SF to activatelipoprotein lipase was compared to normal apoC-II. This indicatesthat major changes in charge around residue 38 lack effect onthe activation properties. The variant may be altered in someother property, such as lipid binding, but since the distributionof apoC-II_SF revealed no simple co-inheritance with lipid levels,it is unclear to what extent it plays a role in the observedhyperlipidemia. The presence of other factors acting togetherwith the variant may predispose to elevated lipid levels.     

The apolipoprotein C-II variant apoC-IILys19→Thr is not associated with dyslipidemia in an affected kindred

The rare apolipoprotein C-II (apoC-II) mutation, apoC-II_Lys19→Thr, also known as apoC-II-v, has been found previously in association with hyperlipoproteinemia. From a lipid clinic screening we identified three unrelated individuals who had the apoC-II_Lys19→Thr mutation. Among eight family members of one proband, we have found another four who were affected. None of the inviduals in this kindred is dyslipidemic and there is no difference in lipid levels between affected and unaffected family members. Therefore, we conclude that the presence of this apolipoprotein variant by itself has no effect on lipoprotein levels. In addition, the apolipoprotein E (apoE) isoform, apoE4 does not have a synergistic effect on lipoprotein levels in this kindred, in contrast to observations on the interaction of apoE4 with another apoC-II mutant (apoC-II_Toronto). The single nucleotide substitution that causes the apoC-II_Lys19→Thr variant introduces a previously unrecognized restriction site (for Mae III), that provides for easy screening.     

Extracoronary atherosclerosis and genetic variants of apolipoprotein AI-CIII cluster in myocardial infarction survivors from southern Italy

The relationships between some genetic markers, as evaluated by DNA analysis, and ultrasound evidence of extracoronary athero-sclerosis, as detected by ultrasound methods, were evaluated in 39 myocardial infarction survivors of middle age and in 40 healthy controls of comparable age. Coronary heart disease (CHD) patients showed higher levels of triglycerides (P = 0.01) and greater number of exsmokers (P = 0.004). Carotid stenoses (> 15%) were detected in ten CHD patients and in two controls; iliac stenoses (> 15%) or abnormal ankle/arm ratio (< 0.97) were found in ten CHD patients and in one control; the scores of vascular disease severity in the myocardial infarction survivors were higher (Mann-Whitney test) than in controls (P < 0.01). Molecular genetic analysis of Sstl restriction fragment length polymorphism (RFLP) of the apolipoprotein (apo) AI-CIII cluster and of the apo B gene demonstrated a higher frequency of the S2 allele (SstI RFLP) in coronary patients than in controls (P = 0.04) and no significant differences in the frequencies of XbaI RFLP of the apo B gene between patients and controls. The relative risk of myocardial infarction associated with an abnormal vascular score (> 8) or with the presence of the rare allele S2 (SstI apo AI-CIII polymorphism) was estimated by odds ratios. The lower 95% limits of odds ratios were above 1 (indicating significant increase in the relative risk of myocardial infarction) both in the case of vascular score and that of SstI RFLP. These associations were independent of one another and of triglyceride levels. SstI RFLP association with CHD disappeared after adjustment for smoking habits. Ultrasound evidence of extracoronary atherosclerosis and SstI RFLP are markers of cardiovascular risk, which might be of help in identifying coronary-prone individuals, independently of the influence of life-style changes or ongoing treatments.Abbreviations apo apolipoprotein - CHD coronary heart disease - HDL high-density lipoprotein - LDL low-density lipoprotein - PCR polymerase chain reactions - RFLP restriction fragment length polymorphism - VLDL very low density lipoprotein Correspondence to: F. De Lorenzo     

Effects of apolipoprotein A-I genetic variations on plasma apolipoprotein,serum lipoprotein and glucose levels

The present authors investigated the individual and combined associations of the apolipoprotein (apo) A-I -75 bp and +83 bp polymorphisms with plasma lipid, lipoprotein and apolipoprotein levels in 734 Caucasian men and women. The frequency of the A allele at position -75 bp (G-->A) was 0.14 in women and 0.17 in men. The frequencies for the rare M2 allele at position +83 bp and/or 84 bp (C-->T and G-->A, respectively) were 0.04 and 0.05 in women and men, respectively. In women, the A allele was associated with significantly higher levels of apo B (P = 0.016), total cholesterol (TC) (P = 0.005), low-density lipoprotein cholesterol (LDL-C) (P = 0.018) and TC:high-density lipoprotein (HDL) ratio (P = 0.026) compared to the G/G subjects. In men, no significant associations were detected between the -75 bp polymorphism and any lipid trait examined. The M2 allele for the +83 bp polymorphism was significantly associated in men with higher levels of apo A-I (P = 0.002) and TC (P = 0.046). In women, a significant effect was observed for TC (P = 0.036), with M2+/- subjects having lower levels than M2+/+ subjects. Significant linkage disequilibrium (P = 0.037) between the apo A-I -75 bp and +83 bp polymorphisms was detected. Women carrying both rare alleles (G/A M2+/-) had significantly higher TC:HDL ratios (P = 0.031) compared to the other haplotypes. In men, significant differences were observed for apo A-I (P = 0.021) and TC (P = 0.044), with carriers of the G/G M2+/- haplotype having the highest values compared to other genotype combinations. In conclusion, the -75 bp (G/A) polymorphism appears to have a significant effect on levels of apo B, plasma TC and LDL-C in women, while the +83 bp polymorphism seems to affect the apo A-I levels in men, and the plasma cholesterol levels in both genders.     

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