Apolipoprotein E Polymorphism and Hyperlipemia in Type II Diabetics

Eto, Masashi; Watanabe, Kiyoshi; Iwashima, Yasunori; Morikawa, Akizuki; Oshima, Eiji; Sekiguchi, Masatomo; Ishii, Kaneo

doi:10.2337/diab.35.12.1374

Cited by 53 publications

(20 citation statements)

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“…18 " 23 However, little information is available on the influence of the apo E phenotype on lipid and lipoprotein concentrations in well-defined specific types of dyslipoproteinemias. Earlier work from our laboratory 1122 suggested that apo E might modulate the phenotypic expression of and/or the susceptibility to hyperiipidemia.…”

Section: Dallongevilk Et Al Apo E Polymorphism In Hyperiipidemiamentioning

confidence: 99%

Apolipoprotein E polymorphism association with lipoprotein profile in endogenous hypertriglyceridemia and familial hypercholesterolemia.

Dallongeville

Roy

LeBoeuf

et al. 1991

Arterioscler Thromb

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Apolipoprotein (apo) E polymorphism was among the first-reported genetic polymorphisms that explained part of the normal variation in plasma cholesterol concentrations in hnmans. The aim of this study was to assess the influence of allelic variation at the apo E gene locus on the plasma lipoprotein profile in hyperlipidemia. The lipoprotein levels of hyperlipidemic subjects of the major apo E phenotypes (E3/2, E3/3, and E4/3) were compared. One hundred eighty-two subjects with endogenous hypertriglyceridemia and 98 subjects with familial hypercholesterolemia due to a 10-kb deletion in their low density lipoprotein (LDL) receptor genes were compared with 424 normolipidemic controls from the same environmental background. LDL concentrations were lower in the E3/2 subset than in the E3/3 or E4/3 subset in the control, hypertriglyceridemic, and familial hypercholesterolemic groups. In absolute values, the magnitude of the effect was greatest in the familial hypercholesterolemic group. However, the direction and percentage change were identical in the presence or absence of the LDL receptor defect, indicating that the apo E phenotype effect is independent of LDL receptor status. Triglyceride and very low density lipoprotein (VLDL) cholesterol concentrations were higher in E3/2 than in E3/3 or E4/3 hypertriglyceridemic subjects, but this difference was not found in the familial hypercholesterolemic or control group. Thus, there seems to be a specific interaction between apo E isoforms and VLDL metabolism in hypertriglyceridemia; allelic variation at the apo E gene locus seems to be associated with specific alterations in the plasma lipoprotein profile of subjects with well-defined types of hyperlipidemia. (Arteriosclerosis and Thrombosis 1991;ll:272-278) P lasma concentrations of lipoproteins, as well as their metabolic fate, are regulated by apolipoproteins (apos) on their surfaces. Among these apos, apo E is a polymorphic protein that determines the catabolism of chylomicron remnants. Three major alleles (e2, e3, and e4) at a single gene locus determine the phenotypic expression of apo E.1 The E2 isoform differs from the most common E3 by a single amino acid substitution in position 158 (Arg-*Cys) of the 299-amino acid chain and displays low-affinity binding to the low density lipoprotein (LDL) receptor in vitro.2 E4 differs from E3 by a single amino acid substitution in position 112 (Cys->Arg) and displays normal affinity for the LDL (B/E) receptor. 3 In vivo, there is evidence that apo E2 carried on triglyceride-rich particles is cleared from plasma more slowly and apo E4 more rapidly than is apo E3.3 - 4The genetic polymorphism of apo E contributes to the normal variation of plasma lipid and lipoprotein concentrations in population studies.5 This has been demonstrated in normolipidemic individuals and in various selected populations.6 -17 Total and LDL cholesterol concentrations are consistently lower in apo E2-bearing subjects, 6 -17 whereas apo E4 is associated with increased LDL cholesterol in a variety of pop...

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Section: Dallongevilk Et Al Apo E Polymorphism In Hyperiipidemiamentioning

confidence: 99%

Apolipoprotein E polymorphism association with lipoprotein profile in endogenous hypertriglyceridemia and familial hypercholesterolemia.

Dallongeville

Roy

LeBoeuf

et al. 1991

Arterioscler Thromb

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“…The presence of the e2 allele results in an accumulation of remnants of triglyceride-rich lipoprotein particles and a decrease in plasma LDL concentration [14]. Because the e2 allele is associated with an increased concentration of triglyceride [15,16] it is a candidate gene for the development of nephropathy. Three small studies in Type I diabetic patients have found conflicting evidence on whether the e2 allele is a risk factor for nephropathy [17,18,19].…”

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confidence: 99%

Differences in HDL-cholesterol:apoA-I + apoA-II ratio and apoE phenotype with albuminuric status in Type I diabetic patients

et al. 2000

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Diabetic nephropathy is associated with cardiovascular morbidity and mortality [1,2]. It is also associated with increased concentrations of serum total and LDL-cholesterol, triglyceride and apolipoprotein (apo)B [3,4,5,6]. In macroalbuminuria HDL-cholesterol is reduced but in microalbuminuric patients HDL-cholesterol has been reported to be reduced [3,4], unchanged [7,8] Abstract Aims/hypothesis. To examine whether the HDL-cholesterol:apoA-I + apoA-II ratio and the e2 allele are related to albuminuria at baseline and whether they are risk factors for progression of albuminuria in a cohort study of patients with Type I (insulin-dependent) diabetes mellitus. Methods. At baseline, the study cohort comprised 617 patients, aged 15±60 years, from seven European diabetic centres of the EURODIAB study. Albumin excretion rate, measured in a central laboratory, was categorised as normoalbuminuria at 20 mg/min or less, microalbuminuria between 20 and 200 mg/min or macroalbuminuria at 200 mg/min or over. Of the 250 patients who were normoalbuminuric at baseline and had follow-up albuminuria measurements, 34 patients were defined as early progressors. Results. At baseline, the mean HDL-cholesterol:apoA-I + apoA-II ratio was lower in macroalbuminuric patients (0.79, 95 % CI:0.74±0.83) compared with normoalbuminuric (0.88, 95 % CI:0.87±0.90) patients (p = 0.0002, adjusted for age and sex). At follow-up, 34 patients who progressed from normoalbuminuria to microalbuminuria or macroalbuminuria also had a slightly lower baseline ratio (0.85, 95 % CI:0.80±0.89) than those 216 who remained normoalbuminuric (0.89, 95 % CI:0.87±0.92) (adjusted p = 0.08). Neither of these relations were independent of LDL-cholesterol or fasting triglyceride. There was no association of the e2 allele with albuminuria either at baseline (OR = 1.4, 95 % CI:0.7±2.8) or with progression of albuminuria (OR = 0.4, 95 % CI:0.1±3.5). Conclusion/interpretation. There is an inverse relation of HDL-cholesterol:apoA-I + apoA-II ratio with albuminuria at baseline. This lower ratio in microalbuminuric or macroalbuminuric patients could contribute to the increased risk of cardiovascular disease associated with nephropathy. There is weak evidence that HDL-composition is a risk factor for progression of albuminuria and no association of the e2 allele with diabetic nephropathy. [Diabetologia 2000

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“…1. The identity of the phenotypes was established by running plasma samples of control apo E phenotypes that had been previously typed using one-or two dimensional gel electrophoresis of ultracentrifuged and delipidated VLDL samples (Eto et al 1985(Eto et al ,1986c. In addition, the identity was also established according to the PI values of apo E isoproteins.…”

Section: Resultsmentioning

confidence: 99%

“…3), and thus, this case was easily judged to be the apo E3/ 3 phenotype. Using this method, we have revaluated the apo E phenotypes in 123 individuals who had been previously classified as either phenotype by our conservative method (Eto et al 1985(Eto et al , 1986c). All were again found to have the same phenotype.…”

Section: Resultsmentioning

confidence: 99%

“…After drying, it was solubilized in 100 p1 of 0.01 mol/liter Tris-HC1 buffer, pH 8.6 with 8 mol/liter urea and 0.01 mol/liter dithiotreitol just before IEF. Some plasma samples were treated with sialidase by the method, as reported previously (Holdsworth et al 1982;Eto et al 1986c). After mixing equal volumes of plasma sample (50 pl) and 0.1 M acetic acid buffer, pH 5.0 (50 p1) and the addition of 10 p1 of 10 U/ml sialidase in acetic acid buffer, incubation was carried out at 3TC for 3 hr.…”

Section: Preparation Of Plasma Samplesmentioning

confidence: 99%

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Apolipoprotein E Phenotyping from Plasma by Isoelectric Focusing and Immunoblotting

Eto

Watanabe

Moriyama

et al. 1990

Tohoku J. Exp. Med.

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A method for apolipoprotein (apo) E phenotyping directly from plasma by isoelectric focusing (IEF) and immunoblotting was confirmed. Ten pl plasma were delipidated. IEF in 5% polyacrylamide flat gel with 6.4 mol/l urea and 2.8% pharmalyte (PH 4-6.5) was carried out at 3,000 V for 1 hr. Seventeen samples were applied per one flat gel, and IEF of two flat gels was made. Then, Western blotting on nitrocellulose membrane was done at 75 V for 3 hr. Immunostaining was performed using goat-anti-human apo E as first antibody and biotinylated anti-goat IgG as second antibody, and 4-chlorodel-l-naphthol as a substrate. In approximately 5% of the samples, we had difficulty in discriminating between homozygotes and heterozygotes (i.e., apo E3/3 and apo E3/2, or apo E4/4 and apo E4/3) because of equally strong sialated band, but this problem was solved by sialidase treatment of plasma before delipidation. As a result, six apo E phenotypes were clearly demonstrated. Apo E phenotyping of 34 samples could be made simultaneously in 2 days. It is concluded that the polyacrylamide gel IEF and immunoblotting method is useful for apo E phenotyping if it is made up for by sialidase treatment. apolipoprotein E ; apolipoprotein E phenotypes ; isoelectric focusing ; immunoblotting

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Apolipoprotein E Polymorphism and Hyperlipemia in Type II Diabetics

Cited by 53 publications

References 0 publications

Apolipoprotein E polymorphism association with lipoprotein profile in endogenous hypertriglyceridemia and familial hypercholesterolemia.

Apolipoprotein E polymorphism association with lipoprotein profile in endogenous hypertriglyceridemia and familial hypercholesterolemia.

Differences in HDL-cholesterol:apoA-I + apoA-II ratio and apoE phenotype with albuminuric status in Type I diabetic patients

Apolipoprotein E Phenotyping from Plasma by Isoelectric Focusing and Immunoblotting

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