Apolipoprotein E2/E2 Genotype in Combination with Mutations in the LDL Receptor Gene Causes Type III Hyperlipoproteinemia
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Jürgen Geisel
Abstract
The primary genetic cause of type III hyperlipoproteinemia is the homozygous presence of the apolipoprotein E2 allele. However, only approximately 1% of subjects with the apolipoprotein E2/E2 genotype develop type III hyperlipoproteinemia. Other factors are therefore necessary to express type III hyperlipoproteinemia. Two individuals were identified as having type III hyperlipoproteinemia (triglyceride to very low-density lipoprotein (VLDL) cholesterol ratio >0.3). However, in contrast to unchanged or slightly decreased low-density lipoprotein (LDL)-cholesterol levels typically observed in type III patients, elevated LDL-cholesterol levels were observed. The expected apolipoprotein E2/E2 isoform was confirmed by genetic analysis. To explain the elevated LDL-cholesterol level, single strand conformation polymorphism analysis was performed to screen for mutations in the LDL receptor gene. In both individuals, mutations causing an impaired LDL receptor function (2 bp insertion in exon 3 and Glu119→Gly mutation in exon 4) were identified. In six more unrelated individuals, these mutations combined with the common apolipoprotein E3/E3 genotype, resulted in an isolated, severe LDLcholesterol elevation. Our results indicate that the level of LDL receptors plays an important role in remnant clearance, and that the combination of the binding-defective apolipoprotein E2 with a defective LDL receptor precipitate type III hyperlipoproteinemia.
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- XV Latin American Congress of Clinical Biochemistry, Florianópolis, Brazil, 1–5 July 2001
- A Method to Detect the G894T Polymorphism of the NOS3 Gene. Clinical Validation in Familial Hypercholesterolemia
- Increasing the Sensitivity of Single-Strand Conformation Polymorphism Analysis of the LDLR Gene Mutations in Brazilian Patients with Familial Hypercholesterolemia
- Hormone Replacement Therapy in Postmenopausal Women and Its Effects on Plasma Lipid Levels
- The Effect of N-Acetylcysteine Supplementation upon Viral Load, CD4, CD8, Total Lymphocyte Count and Hematocrit in Individuals Undergoing Antiretroviral Treatment
- An Evaluation of Antiretroviral Therapy Associated with α-Tocopherol Supplementation in HIV-infected Patients
- Effects of Re-education in Eating Habits and Physical Activity on the Lipid Profile of Obese Teenagers
- Myeloperoxidase-mediated Protein Oxidation: Its Possible Biological Functions
- Novel Haptoglobin Insertion/Deletion Polymorphism Is Associated with the Lipid Profile and C-Reactive Protein (CRP) Concentration
- Apolipoprotein E2/E2 Genotype in Combination with Mutations in the LDL Receptor Gene Causes Type III Hyperlipoproteinemia
- High-Sensitivity Human Thyroglobulin (hTG) Immunoradiometric Assay in the Follow-up of Patients with Differentiated Thyroid Cancer
- Tissue Transglutaminase-Serology Markers for Coeliac Disease
- Serum Adenosine Deaminase and Cytidine Deaminase Activities in Patients with Systemic Lupus Erythematosus
- Effects of Oral N-Acetylcysteine on Plasma Homocysteine and Whole Blood Glutathione Levels in Healthy, Non-pregnant Women
- Evaluating Sequential Values Using Time-adjusted Biological Variation
- High-dose Methylprednisolone Therapy in Multiple Sclerosis Increases Serum Uric Acid Levels
- Evaluation of Accuracy and Uncertainty of ELISA Assays for the Determination of Interleukin-4, Interleukin-5, Interferon-γ and Tumor Necrosis Factor-α
- Development of Immunoturbidimetric Assays for Fourteen Human Serum Proteins on the Hitachi 912™
- Multicenter Evaluation of a Fully Mechanized Soluble Transferrin Receptor Assay on the Hitachi and Cobas Integra Analyzers. The Determination of Reference Ranges
- IFCC News: May/June 2002
- Meetings and Awards
