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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: clinchem.2004.040121v1 51/1/119    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Stephens, J. W. Articles by Humphries, S. E. Search for Related Content PubMed PubMed Citation Articles by Stephens, J. W. Articles by Humphries, S. E. Related Collections Lipids, Lipoproteins, and Cardiovascular Risk Factors

Three Novel Mutations in the Apolipoprotein E Gene in a Sample of Individuals with Type 2 Diabetes Mellitus

¹ Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free & University College London Medical School, London, UK.
² Department of Diabetes & Endocrinology, UCL Hospitals, Mortimer Street, London, UK.
³ Department of Biology, Faculty of Science, Hacettepe University, Ankara, Turkey.
⁴ Department of Vascular Biology, University of Glasgow, Glasgow, UK.

^aAddress correspondence to this author at: British Heart Foundation Laboratories, Royal Free & University College Medical School, Rayne Bldg., 5 University St., London WC1E 6JF, UK. Fax 44-20-7679-6212; e-mail rmhajst{at}ucl.ac.uk.

Background: Apolipoprotein E (apoE) is found in association with triglyceride-rich lipoproteins and is the ligand for the removal of these particles from the plasma. Genetic variations in exon 4 lead to three common gene variants: E2, E3, and E4.

Methods: We performed apoE genotyping in 765 individuals with type 2 diabetes.

Results: We identified three new variant heteroduplex patterns. Sequencing of these variants revealed three novel mutations that were related to biochemical and clinical characteristics. One mutation produced a frameshift at amino acid position 166, which predicted termination of protein synthesis. This individual had a heteroduplex pattern and sequence of E3E3, which was associated with a change in the plasma isoelectric focusing pattern and a 70% lower plasma concentration of apoE compared with healthy individuals. The other mutations were both single base changes. A CGC>CAC change at amino acid position 150 predicted a substitution of Arg>His. This individual had a heteroduplex pattern and sequence of E2E2, which was not associated with major changes in plasma lipids or apoE concentration. The third individual had a CGC>CCC base change at amino acid position 114, which predicted an Arg>Pro change. This person had a heteroduplex pattern and sequence of E3E3, higher plasma total cholesterol, and moderately decreased plasma apoE.

Conclusions: The frequency of new mutations in this sample (1 in 255) is higher than that of a healthy population (1 in 7900). Further screening for common apoE gene variants in individuals at risk for dyslipidemia may reveal abnormal heteroduplex patterns and uncover further mutations in this important lipid-regulating gene.

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				L. M. Silverman and T. M. Mifflin Genotype-Phenotype Correlations (II): Assessing the Influence of Sequence Variants on the Clinical Phenotype in Multifactorial Disorders Clin. Chem., June 1, 2005; 51(6): 929 - 930. [Full Text] [PDF]

				L. M. Silverman and M. S. Mahadevan Genotype-Phenotype Correlations: Assessing the Influence of Sequence Variants on the Clinical Phenotype Clin. Chem., January 1, 2005; 51(1): 8 - 8. [Full Text] [PDF]