HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI 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 ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Baron, H. Articles by Schuster, H. Search for Related Content PubMed PubMed Citation Articles by Baron, H. Articles by Schuster, H. Related Collections Molecular Diagnostics and Genetics Lipids, Lipoproteins, and Cardiovascular Risk Factors

Oligonucleotide Ligation Assay for Detection of Apolipoprotein E Polymorphisms

¹ Applied Biosystems Div. of Perkin-Elmer, Foster City, CA;
^a address for correspondence: Franz Volhard Clin., Wiltberg Str. 50, 13122 Berlin, Germany, fax 0049 30 9417 2206, e-mail fcluft@mdc-berlin.de

Apolipoprotein (apo) E is a protein component of lipoproteins, 50% of which resides in HDL, 10% in LDL, 20% in IDL, and 20% in VLDL cholesterol fractions (1). Apo E binds to the LDL receptor, also termed the B,E receptor, because the receptor accepts both apo B and apo E. Apo E is also thought to bind to a specific chylomicron remnant receptor by virtue of its structural determinants. The heterogeneity in receptor binding of different varieties of apo E is explained by the affinity of different apo E alleles to various receptors. Apo E polymorphisms may be explained by three major alleles: apo E2, apo E3, and apo E4, which are found in 10%, 76%, and 13%, respectively, of the Caucasian population (2). The polymorphisms are due to substitution of a cysteine for an arginine at residue 112 or 158, or at both residues. The apo E2 variant has the lowest affinity for the LDL receptor. There is an LDL concentration gradient in both the healthy population and in those with coronary heart disease. Individuals homozygous for apo E2 have the lowest concentrations of LDL, and apo E4 homozygotes have the highest LDL concentrations (3). The apo E4 allele has also been associated with Alzheimer disease. However, the mechanisms of this association are not yet clear (4). Thus, the interest in apo E polymorphisms is high, both on the basis of epidemiological research and for the purpose of clarifying individual lipid disturbances or dementias. We have successfully applied the oligonucleotide ligation assay (OLA) technique to screen for mutations causing familial hypercholesterolemia (5). We have now adapted this technique for the detection of apo E polymorphisms in large numbers of samples.

PCR amplification . . . [Full Text of this Article]

Acknowledgments

Footnotes

References

The following articles in journals at HighWire Press have cited this article:

				E. E. Niederkofler, K. A. Tubbs, U. A. Kiernan, D. Nedelkov, and R. W. Nelson Novel mass spectrometric immunoassays for the rapid structural characterization of plasma apolipoproteins J. Lipid Res., March 1, 2003; 44(3): 630 - 639. [Abstract] [Full Text] [PDF]

				N. Jacobsen, J. Bentzen, M. Meldgaard, M. H. Jakobsen, M. Fenger, S. Kauppinen, and J. Skouv LNA-enhanced detection of single nucleotide polymorphisms in the apolipoprotein E Nucleic Acids Res., October 1, 2002; 30(19): e100 - e100. [Abstract] [Full Text] [PDF]

				M. Nauck, M. M. Hoffmann, H. Wieland, and W. Marz Evaluation of the Apo E Genotyping Kit on the LightCycler, Clin. Chem., May 1, 2000; 46(5): 722 - 724. [Full Text] [PDF]

				E.-L. Romppanen and I. Mononen PCR-Oligonucleotide Ligation Assay from Dried Blood Spots Clin. Chem., November 1, 1999; 45(11): 2022 - 2025. [Full Text] [PDF]

				G. G. Donohoe, A. Salomaki, T. Lehtimaki, K. Pulkki, and V. Kairisto Rapid Identification of Apolipoprotein E Genotypes by Multiplex Amplification Refractory Mutation System PCR and Capillary Gel Electrophoresis Clin. Chem., January 1, 1999; 45(1): 143 - 146. [Full Text] [PDF]