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At least 19 recordsLinked to original sources
PubMed1992

The functional characteristics of a human apolipoprotein E variant (cysteine at residue 142) may explain its association with dominant expression of type III hyperlipoproteinemia.

Type III hyperlipoproteinemia typically is associated with homozygosity for apolipoprotein (apo) E2(Arg158----Cys). Dominant expression of type III hyperlipoproteinemia associated with apoE phenotype E3/3 is caused by heterozygosity for a human apoE variant, apoE3(Cys112----Arg, Arg142----Cys). However, this apoE3 variant was not separable from the normal apoE3 in these patients' plasma because the two proteins have identical amino acid composition, charge, and molecular weight. Therefore, to determine the functional characteristics of this protein, we used recombinant DNA techniques to produce this apoE variant in bacteria. We also produced a non-naturally occurring variant, apoE(Arg142----Cys), that had only the cysteine substituted at residue 142. These two apoE variants were purified from cell lysates of the transfected Escherichia coli by ultracentrifugal flotation in the presence of phospholipid, by gel filtration chromatography, and by heparin-Sepharose chromatography. Both Cys142 apoE variants bound to lipoprotein receptors on human fibroblasts with only about 20% of normal binding activity. Therefore, cysteine at residue 142, not arginine at residue 112, is responsible for the decreased receptor binding activity of the variants. Cysteamine treatment and removal of the carboxyl-terminal domain had little effect on the binding activity, whereas both modulate the receptor binding activity of apoE2(Arg158----Cys). The mutation at residue 142 decreased the binding activity of apoE to both heparin and the monoclonal antibody 1D7 (this antibody inhibits receptor binding of apoE), whereas apoE2(Arg158----Cys), which is associated with recessive expression of type III hyperlipoproteinemia, binds normally to both. The Arg112, Cys142 variant predominantes 3:1 over normal apoE3 in the very low density lipoproteins of plasma from an affected subject, as assessed by differential reactivity with the antibody 1D7. The unique combination of functional properties of the Arg112, Cys142 variant provides a possible explanation for its association with dominant expression of type III hyperlipoproteinemia.

Amino Acid Sequence↗
PubMed1994

Comparative effects of gemfibrozil and clofibrate in type III hyperlipoproteinemia.

Type III hyperlipoproteinemia (dysbetalipoproteinemia) is characterized by elevated concentrations of plasma cholesterol and triglycerides due to an increase in very low density lipoprotein (VLDL) remnant lipoproteins. In a retrospective analysis we observed that in 12 patients with this disorder, gemfibrozil reduced concentrations of total cholesterol, VLDL cholesterol and triglycerides by 48%, 72% and 68%, respectively. These changes were greater than those reported in a similar number of patients treated with clofibrate. Comparative data on the efficacy of different fibrates in this disorder are very limited; to assess this further we have compared the hypolipidemic effects of gemfibrozil (600 mg twice daily) and clofibrate (1 g twice daily) in six patients with well-characterized type III hyperlipoproteinemia. Baseline values were obtained after at least 8 weeks on diet and treatment values were obtained after 6 and 8 weeks of treatment with each drug. Treatment with clofibrate and gemfibrozil both resulted in significant reductions in the plasma concentrations of total cholesterol (40% and 54%), VLDL cholesterol (59% and 79%) and total triglycerides (48% and 70%), as well as a significant increase in HDL cholesterol (9% and 7%). Gemfibrozil was, however, significantly (P < 0.05) more effective in reducing plasma concentrations of total cholesterol, VLDL cholesterol and triglycerides than was clofibrate, in the same patients.

Adult↗
PubMed1996

Apo E variants in patients with type III hyperlipoproteinemia.

Type III hyperlipoproteinemia (HLP III) is characterized by the reduced catabolism and accumulation of chylomicron and very low density lipoprotein (VLDL) remnants. Most HLP III patients are homozygous for the apolipoprotein E2 (Cys112, Cys158) allele; however, several other mutations at this gene locus have been associated with this HLP. In order to assess the presence of rare apo E variants in our population, we have examined apo E phenotypes by isoelectric focusing (IEF) and genotypes by restriction enzyme analysis of polymerase chain reaction (PCR) amplified DNA in 15 patients with HLP III. Lack of concordance between these two methods was observed in 11 subjects (73.3%). DNA sequencing analysis of the receptor binding domain of the apo E gene in the 11 HLP III patients with discrepancies demonstrated the presence of six carriers of the epsilon 3(Arg136-->Ser) allele and three carriers of the epsilon 2(Gly127-->Asp) allele. Five HLP III patients were apo E2/E2 using IEF, but only 2 of them were epsilon 2 homozygous using PCR. Two patients were E3/E3 homozygous with normal DNA sequence in the low density lipoprotein receptor binding domain of apo E. In conclusion, our results show that a number of different apo E genotypes are associated with HLP III in this population. More specifically, mutations at positions 127 and 136 might be frequent in Spain and occur in patients with HLP III.

Adolescent↗
PubMed1997

Comparative effects of bezafibrate and micronised fenofibrate in patients with type III hyperlipoproteinemia.

Type III hyperlipoproteinemia (HLP) is characterized by elevated concentrations of plasma cholesterol and triglycerides due to an increase in atherogenic beta-very low density lipoproteins (beta-VLDL). As a consequence, affected individuals develop premature and accelerated atherosclerosis. Fibrates have been shown to be most effective in treatment of the dyslipidemia in type III HLP. However, comparative data on the efficacy of different fibrates in this disorder are very limited; to assess this further we have compared in a prospective study the hypolipidemic effects of bezafibrate (400 mg once daily) and micronised fenofibrate (200 mg once daily) in 23 patients with well-characterized type III HLP. Baseline values were obtained after 4 weeks on diet and treatment values were obtained after 12 weeks of treatment with each drug. Treatment with bezafibrate and micronised fenofibrate both resulted in significant reductions in the serum concentrations of total cholesterol (26.0% and 38.7%), VLDL cholesterol (41.5% and 54.1%) and total triglycerides (27.5% and 39.1%), as well as a significant increase in high density lipoprotein (HDL) cholesterol (15.0% and 27. 8%). Micronised fenofibrate was, however, significantly (P < 0.05) more effective in reducing serum concentrations of total cholesterol and VLDL cholesterol and increasing HDL cholesterol than was bezafibrate in the same patients.

Bezafibrate↗
PubMed1996

A 10-bp deletion in the apolipoprotein epsilon gene causing apolipoprotein E deficiency and severe type III hyperlipoproteinemia.

Type III hyperlipoproteinemia (HLP) is usually associated with homozygosity for apolipoprotein (apo) E2. We identified a 30-year-old male German of Hungarian ancestry with severe type III HLP and apo E deficiency. The disease was expressed in an extreme phenotype with multiple cutaneous xanthomas. Apo E was detectable only in trace amounts in plasma but not in the different lipoprotein fractions. Direct sequencing of PCR-amplified segments of the apo epsilon gene identified a 10-bp deletion in exon 4 (bp 4037-4046 coding for amino acids 209-212 of the mature protein). The mutation is predictive for a reading frameshift introducing a premature stop codon (TGA) at amino acid 229. By western blot analysis, we found small amounts of a truncated apo E in the patient's plasma. Family analysis revealed that the proband was homozygous--and 10 of 24 relatives were heterozygous--for the mutation. Heterozygotes had, as compared to unaffected family members, significantly higher triglycerides (TG), very low-density lipoprotein (VLDL) cholesterol and a significantly higher VLDL cholesterol-to-serum TG ratio, which is indicative of a delayed remnant catabolism. We propose that the absence of a functionally active apo E is the cause of the severe type III HLP in the patient and that the mutation, even in a single dose in heterozygotes, predisposes in variable severity to the phenotypic expression of the disease.

Adolescent↗
PubMed1988

Further resolution and comparison of the heterogeneity of plasma low-density lipoproteins in human hyperlipoproteinemias: type III hyperlipoproteinemia, hypertriglyceridemia and familial hypercholesterolemia.

The heterogeneity of the plasma low-density lipoproteins (LDL) in subjects with type III hyperlipoproteinemia (3 cases), with hypertriglyceridemia (4 cases) and with the heterozygous form of familial hypercholesterolemia (FH, 4 cases) has been evaluated using a new, high resolution equilibrium density gradient ultracentrifugation procedure. The mass distribution profile, physicochemical properties, particle heterogeneity and apoprotein B content of a series of 13 LDL subfractions was examined in the 3 hyperlipidemic groups and the data were compared with those reported earlier in normolipidemic subjects. In FH, LDL mass was distributed as a narrow peak of d approximately 1.031-1.034 g/ml, whereas the distribution in hypertriglyceridemia was markedly asymmetric with a single peak of elevated density (d approximately 1.037-1.043 g/ml); the distribution in type III subjects was distinguished by its bi- or trimodal nature and broad profile. The chemical composition of LDL gradient subfractions in FH and in hypertriglyceridemia markedly resembled that of the respective parent LDL of d = 1.019-1.063 g/ml, displaying elevated proportions of cholesteryl ester in FH and of protein in hypertriglyceridemia. LDL subfractions in type III disease were enriched in free cholesterol. The Stokes diameters of LDL particles in corresponding subfractions from the 3 hyperlipidemic states were similar; however, whereas a single particle species was characteristic of each LDL subfraction in both FH and in our normolipidemic group, 2 species were frequently present in each subfraction in both type III and type IV diseases; in addition, subfractions from type III subjects occasionally exhibited 3 size species. Apolipoprotein B-100 was the predominant protein component in LDL subfractions from all 3 hyperlipidemic groups. Plasma LDL consist then of multiple particle species which constitute a particularly complex spectrum in type III hyperlipoproteinemia and in hypertriglyceridemia. The origin(s) of such particle subspecies is indeterminate at present; moreover, they may differ in their intravascular metabolism, in their degradation in tissues and in their relative atherogenicities.

Adolescent↗
PubMed1976

Pediatric familial type III hyperlipoproteinemia.

Familial type III hyperlipoproteinemia is almost always first diagnosed in adults; the two 16-yr-old probands with type III in this report represent only the fifth and sixth children reported with the disorder. S.E., a 16-yr-old female, and C.H., a 21-yr-old male, (with palmar xanthomas at age 16) had beta-migrating abnormal very low density lipoproteins (beta-VLDL), density less than 1.006. S.E.'s brother (age 21) and mother (age 57) had type III; her grandmother had beta-VLDL and elevated triglycerides, and a maternal uncle had type IV hyperlipoproteinemia. C.H.'s father had type III; a sister and paternal aunt had type IV hyperlipoproteinemia. It is important to consider the diagnosis of type III hyperlipoproteinemia in the pediatric age group, particularly in children from families with type III hyperlipoproteinemia.

Adolescent↗
PubMed1999

Comparison of the hypolipidemic effect of gemfibrozil versus simvastatin in patients with type III hyperlipoproteinemia.

BACKGROUND: Type III hyperlipoproteinemia is characterized by the accumulation of chylomicron and very low density lipoprotein (VLDL) remnants. Individuals with this disorder have a high risk of premature atherosclerosis, and hypolipidemic drugs are useful in their management. METHODS: We compared, in a double-blind, placebo-controlled, randomized crossed study, the effects of gemfibrozil (1200 mg/day) and simvastatin (20 mg/day) on lipids, apolipoprotein AI, apolipoprotein B, and apolipoprotein E and on lipids and apolipoprotein B content in VLDL, intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in 10 patients with type III hyperlipoproteinemia. RESULTS: Levels of total cholesterol, VLDL cholesterol, IDL cholesterol, and apolipoprotein B decreased with both drugs. Larger reductions in triglycerides (109 +/- 28.2 mg/dL, P =.005), VLDL cholesterol (24.7 +/- 10.9 mg/dL, P =.05), and VLDL triglycerides (86.3 +/- 20.2 mg/dL, P =.003) were obtained with gemfibrozil compared with simvastatin. LDL cholesterol reduction was more effective with simvastatin than with gemfibrozil (44.3 +/- 17.1 mg/dL, P =.03). HDL cholesterol after gemfibrozil was 5.71 +/- 2.37 mg/dL higher than after simvastatin. CONCLUSIONS: In patients with type III hyperlipoproteinemia gemfibrozil is more effective in reducing total triglyceride and VLDL lipid levels than simvastatin, and simvastatin is better in reducing LDL cholesterol than gemfibrozil is. IDL and apolipoprotein E levels were reduced similarly with both drugs.

Adult↗
PubMed1977

Evaluation of the classical methods for the diagnosis of type III hyperlipoproteinemia.

Familial type III hyperlipoproteinemia is characterized by the presence of elevated plasma levels of very low density lopoproteins (VLDL) which contain an increased amount of cholesterol and by the presence of a significant amount of lipoproteins with an intermediate density between that of VLDL and low density lipoproteins (LDL); the intermediate density lopoproteins, designated IDL or Lp III, have a slower electrophoretic migration rate than VLDL, and are found in the ultracentrifugal top fraction as a contaminant. Classically, the diagnosis of type III is based on the demonstration of beta-migrating lipoproteins in the ultracentrifugal top fraction (density less than 1.006), thus "floating beta-lipoprotein". More recently, it has been proposed that an elevated VLDL-cholesterol to triglyceride ratio is diagnostic of the disorder. In the present report, we have compared the two methods for their diagnostic value and have concluded that the chemical index definition is the more reliable method for the diagnosis of type III hyperlipoproteinemia.

Electrophoresis, Paper↗
PubMed1997

The apolipoprotein E2 (Arg145Cys) mutation causes autosomal dominant type III hyperlipoproteinemia with incomplete penetrance.

Type III hyperlipoproteinemia (type III HLP) is an atherogenic disorder of lipoprotein metabolism characterized by the accumulation of cholesterol-enriched VLDL and is usually associated with homozygosity for a normal variant of apoE, apoE2. ApoE2(Arg145Cys) is a rare variant arising from a C-->T transition at nucleotide 4031 and has been linked to type III HLP. Ten subjects from a group of 42 unrelated individuals with proven type III HLP were found to be either heterozygous or homozygous for the apoE2(Arg145Cys) mutation by DNA sequencing. The apoE4-Philadelphia (Glu13Lys, Arg145Cys) variant was subsequently excluded. None of 4 homozygotes (3 blacks and 1 of mixed ancestry) developed ischemic heart disease, but they did present with xanthomata. In contrast, 6 heterozygous subjects presented mainly with ischemic heart disease but generally lacked physical signs. Cholesterol concentrations ranged from 6.2 mmol/L to 13.3 mmol/L and triglyceride levels from 3.2 to 13.2 mmol/L. The dyslipoproteinemia in homozygous and heterozygous subjects was indistinguishable. Family investigation identified an additional 10 heterozygous mutant-allele carriers, of whom 3 had type III HLP. This unique cohort of patients indicates that the apoE2(Arg145Cys) mutation is relatively common in several population groups in our region and may be particularly prevalent in blacks. There was no clear allele dosage effect present for the development of dyslipoproteinemia or atherosclerosis. The mode of inheritance is for the first time clearly established to be autosomal dominant with incomplete penetrance.

Adolescent↗
PubMed1991

Lathosterol level in plasma is elevated in type III hyperlipoproteinemia, but not in non-type III subjects with apolipoprotein E2/2 phenotype, nor in type IIa or IIb hyperlipoproteinemia.

We measured the serum lathosterol level, a reflection of the rate of whole body cholesterol synthesis, in 15 patients with manifest type III hyperlipoproteinemia (HLP), in 20 subjects with apolipoprotein (apo) E2/2 phenotype, but without type III HLP, in 21 patients with type IIA and 10 patients with type IIB HLP. A group of 100 subjects with apo E3/3 phenotype served as reference. Using ANCOVA, lathosterol was adjusted for serum cholesterol and triglyceride concentrations, since these parameters were found to independently correlate with lathosterol. The adjusted means (+/- SEM), in mumol/L, in these groups were 12.9 +/- 1.1, 8.2 +/- 1.1, 4.8 +/- 0.9, 9.8 +/- 1.4, and 7.8 +/- 0.4, respectively. Type III HLP patients had significantly higher lathosterol levels than all other groups except type IIB HLP. In addition, lathosterol was significantly lower in type IIA patients than in all other groups. The serum levels of plant sterols, used as a reflection of cholesterol absorption, did not differ among the various groups after adjustment for serum cholesterol. These findings suggest that an overproduction of cholesterol is one factor discriminating E2/2 homozygotes with type III HLP from those without the disease.

Analysis of Variance↗
PubMed1993

[Apolipoprotein E phenotyping--useful in the study of hyperlipoproteinemia type III].

Apolipoprotein E (apo E) is a protein constituent of several plasma lipoproteins. Its major physiological role is to mediate the interaction of these lipoproteins and receptors. Three common apo E alleles and six phenotypes are known. The phenotype E2/E2 is associated with type III hyperlipoproteinemia. As a consequence of the increasing clinical interest in apo E phenotypes, especially in relation to the diagnosis of type III hyperlipoproteinemia, we have established a method for apo E phenotyping. Allele frequencies from a population of 211 healthy individuals are presented. The results show that, like as in Finland and Sweden the e4 allele is more frequent than in non-Nordic countries.

Adult↗
PubMed1999

Ratio of remnant-like particle-cholesterol to serum total triglycerides is an effective alternative to ultracentrifugal and electrophoretic methods in the diagnosis of familial type III hyperlipoproteinemia.

BACKGROUND: Familial type III hyperlipoproteinemia (HLP) is characterized by the presence of beta-migrating VLDL (beta-VLDL) and increased risk of cardiovascular disease. Assessment of plasma beta-VLDL is achieved by measuring the ratio of VLDL-cholesterol (VLDL-C) to total plasma triglycerides (TGs) or by detecting beta-VLDL in total VLDL. The objective of this study was to compare the clinical utility of the ratio of remnant-like particle-cholesterol (RLP-C) to total TGs with that of the current methods for diagnosing type III HLP. METHODS: Detection of beta-VLDL by electrophoresis of VLDL was used to define type III HLP. Twenty-eight patients with type III HLP and 43 subjects lacking beta-VLDL were investigated. Fasting TG concentrations were >2.26 mmol/L in all subjects. Subjects were separated into three groups: group 1, serum total cholesterol </=5.18 mmol/L (n = 11); group 2, total cholesterol >5.18 mmol/L and TGs between 2.26 and 9.04 mmol/L (n = 51); and group 3, TGs >9.04 mmol/L (n = 9). RESULTS: In group 2, a RLP-C-to-total TG molar ratio >/=0.23 (>/=0.10 when using mg/dL) and a VLDL-C-to-total TG molar ratio >/=0.69 (>/=0.30 when using mg/dL) correctly classified 94% and 90% of the subjects, respectively. The utility of the RLP-C-to-total TG ratio in diagnosing type III HLP decreased in patients in the other two groups. CONCLUSION: When used in an appropriate target population, the RLP-C-to-total TG ratio is a convenient and effective alternative to ultracentrifugal and electrophoretic methods for diagnosing type III HLP.

Apolipoproteins↗
PubMed1998

Molecular basis of type III hyperlipoproteinemia in Germany.

Type III hyperlipoproteinemia (HLP) is usually associated with homozygosity for apolipoprotein (apo) E2 (Arg112 --> Cys, Arg158 --> Cys). This common apo E isoform is defective in its binding to lipoprotein receptors. However, other rare mutations in the apo epsilon gene may also, in part dominantly, predispose to the disease. In order to assess the prevalence of rare apo E variants and mutations in the apo epsilon gene in Germany, we examined apo epsilon genotypes by restriction isotyping (RI) and apo E phenotypes by isoelectric focusing (IEF) in 107 German patients with type III HLP. Concordance between apo epsilon genotype and apo E phenotype was observed in 101 subjects (94.4%). Six individuals (5.6%) had genotypes and phenotypes other than E2/2. One subject was apparently homozygous for apo E2 by IEF, but heterozygous for epsilon3/2 by RI. Sequencing of the apo epsilon gene disclosed a hitherto undescribed point mutation (TGG --> TGA) at the third position of the codon for amino acid 20 (Trp), introducing a premature termination codon. This is the first study demonstrating that in the German population type III HLP is mainly associated with homozygosity for apo E2 (Arg112 --> Cys, Arg158 --> Cys) and that discrepancies between apo epsilon genotype and apo E phenotype are rare in this genetic condition.

Adult↗
PubMed1990

Simvastatin in the effective reduction of plasma lipoprotein levels in familial dysbetalipoproteinemia (type III hyperlipoproteinemia).

PURPOSE: Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) is characterized by an increase of serum lipids caused by an accumulation of remnant particles of triglyceride-rich lipoproteins. We studied the efficacy of simvastatin, an inhibitor of the biosynthesis of cholesterol, in this disorder. PATIENTS AND METHODS: Twelve patients participated in an open-label study. After a three-week placebo period, they were treated with increasing doses (10 mg twice a day, 20 mg twice a day, and 40 mg twice a day) of simvastatin in six-week periods. RESULTS: With the 80-mg dose, the mean serum cholesterol level decreased from 12.30 +/- 4.96 to 5.29 +/- 1.24 mmol/L (mean reduction, 54%) and the mean serum triglyceride level decreased from 8.77 +/- 7.16 to 3.61 +/- 1.33 mmol/L (-48%); this was due to a decrease in very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) lipids. There was a decrease in the ratio of VLDL cholesterol to serum triglycerides and in the apolipoproteins B and E, suggesting a reduction in the amount of circulating atherogenic remnant particles. Except for a slight increase in serum alanine aminotransferase levels in three patients, no side effects were observed. CONCLUSION: These data show that levels of serum lipids can be effectively reduced by simvastatin in familial dysbetalipoproteinemia.

Adult↗
PubMed1989

High receptor binding affinity of lipoproteins in atypical dysbetalipoproteinemia (type III hyperlipoproteinemia).

Familial dysbetalipoproteinemia (or type III hyperlipoproteinemia) is characterized by the presence of abnormal, cholesteryl ester-rich beta-very low density lipoproteins (beta-VLDL) in the plasma. Subjects with typical dysbetalipoproteinemia are homozygous for an amino acid substitution in apolipoprotein (apo-) E at residue 158 and have defective apo-E-mediated binding of both pre-beta-VLDL and beta-VLDL to apo-B,E(LDL) (or LDL) receptors (1988. Chappell, D.A., J. Clin. Invest. 82:628-639). To understand the effect of substitutions in apo-E at sites other than residue 158, nine dysbetalipoproteinemic (dys-beta) subjects who were either homozygous or heterozygous for substitutions in apo-E at atypical sites were studied. These substitutions occurred at residue 142 (n = 6), 145 (n = 2), or 146 (n = 1) and are known to cause less defective binding than does the 158 substitution. The chemical composition and electrophoretic mobility of pre-beta-VLDL and beta-VLDL from atypical and typical dys-beta subjects were indistinguishable. However, lipoproteins from atypical and typical dys-beta subjects differed in their affinity for the apo-B,E(LDL) receptor on cultured human fibroblasts. The pre-beta-VLDL and beta-VLDL from atypical dys-beta subjects had 640- or 17-fold higher affinity, respectively, than did corresponding lipoproteins from typical dys-beta subjects. The higher binding affinity of lipoproteins from atypical dys-beta subjects was associated with a higher ratio of apo-E to total apo-C. Since higher binding affinity should cause more rapid receptor-mediated clearance of beta-VLDL in atypical than in typical dys-beta subjects in vivo, the mechanism of beta-VLDL accumulation may differ in these two groups.

Adolescent↗
PubMed2003

Apolipoprotein epsilon 2/3 genotype and type III hyperlipoproteinemia among Taiwanese.

BACKGROUND: Type III hyperlipoproteinemia (HLP) is a genetic disorder of lipid metabolism in humans that predisposes affected subjects to the premature development of atherosclerosis. Most type III HLP occurs in homozygous carriers of apolipoprotein (apo) E2. The aims of this study were to determine the frequencies of different apo E genotypes in type III HLP in Taiwanese and to assess the possibility of apo E mutants in these patients. MATERIALS AND METHODS: Four hundred and seven patients with hyperlipoproteinemia were recruited. Electrophoresis, apo E genotyping and sequencing were performed. RESULTS: Of the 407 hyperlipoproteinemia, 8 were identified as type III HLP. In contrast to reports of high apo epsilon 2/2 genotype prevalence, only two of the type III HLP subjects were of the apo epsilon 2/2 genotype (25%). Fifty percent of the type III HLP were of apo epsilon 2/3 genotype. This observation was further reflected in a lower frequency of the epsilon 2 allele (0.563) and higher epsilon 3 allele (0.375) frequency. No rare apo E variant was found by direct sequencing. CONCLUSION: The most common genotype of type III HLP in Taiwan was apo epsilon 2/3 instead of apo epsilon 2/2.

Aged↗
PubMed1982

Studies of familial type III hyperlipoproteinemia using as a genetic marker the apoE phenotype E2/2.

Clinical symptoms, lipoprotein patterns, and apoE phenotypes were determined in 17 individuals with type III hyperlipoproteinemia (type III HLP) and in their relatives and spouses. The apoE phenotype E2/2 occurred in 15 type III HLP probands (88%) and the apoE phenotype E4/2 was found in 2 probands. In each of the families studied, the apoE phenotype inheritance was compatible with a model we previously proposed in which apoE is determined at a single genetic locus with three common alleles. The apoE phenotypes E4/4, E3/3, and E2/2 represent homozygosity for the apoE alleles epsilon4, epsilon3, and epsilon2, respectively, whereas the apoE phenotypes E4/3, E3/2, and E4/2 represent heterozygosity for the apoE alleles epsilon4/epsilon3, epsilon3/epsilon2, and epsilon4/epsilon2, respectively. Plasma lipids in 69 relatives of type III HLP probands were analyzed by apoE phenotype and revealed no significant differences between phenotypes in the levels of cholesterol, triglyceride, or HDL cholesterol. However, there were differences between the apoE phenotypes in LDL cholesterol levels (P = 0.01) and in the ratio of VLDL cholesterol/total triglyceride (ratio) (P < 0.01). Relatives with the apoE phenotype E2/2 had the lowest LDL cholesterol levels and the highest ratios. Of these eleven individuals with the apoE phenotype E2/2 who were not type III HLP probands, two males were taking lipid-lowering drugs, one male had mild angina at age 59, five individuals had ratios >0.25 and two had ratios >0.30 with the ratios for males (0.28 +/- 0.06) significantly greater than the ratios for females (0.17 +/- 0.06) (P < 0.01), and seven had evidence of floating betaVLDL on lipoprotein electrophoresis. In addition, when compared to a control group in the general population, the whole group of relatives had normal cholesterol and HDL cholesterol levels, slightly low LDL cholesterol levels, and almost twice elevated triglyceride levels. In summary, a) a very strong but not invariate association exists between type III HLP and the apoE phenotype E2/2 with some type III HLP individuals having the apoE phenotype E4/2; b) apoE phenotype inheritance is determined by three alleles at a single genetic locus; c) relatives of type III HLP probands, no matter what their apoE phenotype, have on the average nearly twofold elevated plasma triglyceride levels compared to a control population; and d) non-proband type III HLP individuals with the apoE phenotype E2/2 have been identified. As a group these individuals, particularly the males, show a tendency to express type III HLP, but clearly genetic or environmental factors other than the apoE phenotype E2/2 are required for the full phenotypic expression of this disease.-Breslow, J. L., V. I. Zannis, T. R. SanGiacomo, J. L. H. C. Third, T. Tracy, and C. J. Glueck. Studies of familial type III hyperlipoproteinemia using as a genetic marker the apoE phenotype E2/2.

Adult↗