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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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TaqMan Systems for Genotyping of Disease-Related Polymorphisms Present in the Gene Encoding Apolipoprotein E

Werner Koch / Angela Ehrenhaft / Korinna Griesser / Arne Pfeufer / Jakob Müller / Albert Schömig / Adnan Kastrati

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 40, Issue 11, Pages 1123–1131, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm.2002.197, June 2005

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Polymorphisms of the gene encoding apolipoprotein E have been implicated in the pathogenesis of peripheral and coronary artery disease and neurodegenerative disorders such as sporadic and late-onset familial forms of Alzheimer's disease. We have developed TaqMan assay systems for the single nucleotide polymorphisms −219G/T, located in the promoter of the apolipoprotein E gene, 113G/C, present in the transcriptional enhancer element of intron 1, 334T/C, determining Cys or Arg as amino acid residue 112 of mature apolipoprotein E, and 472C/T, determining Arg or Cys as residue 158. The accuracy of genotype determination with the TaqMan systems was demonstrated by analyses with restriction endonucleases. We determined the genotypes of the apolipoprotein E polymorphisms in 2349 study subjects. The genotypes were distributed as: −219GG=27.3%, −219GT=49.1%, and −219TT=23.6% (p=0.435); 113GG=41.3%, 113GC=45.2%, and 113CC=13.5% (p=0.343); 334TT=73.4%, 334TC=24.7%, and 334CC=1.9% (p=0.539); 472CC=86.3%, 472CT=12.8%, and 472TT=0.9% (p=0.004) (Hardy-Weinberg equilibrium estimates are given in parentheses). The allele combinations which define the three major isoforms of apolipoprotein E, namely apoE2, apoE3, and apoE4, had the following allele frequencies: 334T/472T (∊2; 112Cys/158Cys)=7.3%, 334T/472C (∊3; 112Cys/158Arg)=78.4%, and 334C/472C (∊4; 112Arg/158Arg)=14.2%, respectively. ApoE genotypes were distributed as: ∊2∊2=0.9%, ∊2∊3=11.2%, ∊2∊4=1.6%, ∊3∊3=61.3%, ∊3∊4=23.1%, and ∊4∊4=1.9% (p=0.014). The TaqMan assays allow for fast and sensitive genotyping and are especially suitable for studies including large numbers of participants.

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