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Molecular basis of type III hyperlipoproteinemia in Germany
Author(s) -
Feussner Giso,
Feussner Vera,
Hoffmann Michael M.,
Lohrmann Jens,
Wieland Heinrich,
März Winfried
Publication year - 1998
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1998)11:6<417::aid-humu1>3.0.co;2-5
Subject(s) - biology , type (biology) , genetics , computational biology , ecology
Type III hyperlipoproteinemia (HLP) is usually associated with homozygosity for apolipoprotein (apo) E2 (Arg 112 → Cys, Arg 158 → Cys). This common apo E isoform is defective in its binding to lipoprotein receptors. However, other rare mutations in the apo ϵ gene may also, in part dominantly, predispose to the disease. In order to assess the prevalence of rare apo E variants and mutations in the apo ϵ gene in Germany, we examined apo ϵ genotypes by restriction isotyping (RI) and apo E phenotypes by isoelectric focusing (IEF) in 107 German patients with type III HLP. Concordance between apo ϵ genotype and apo E phenotype was observed in 101 subjects (94.4%). Six individuals (5.6%) had genotypes and phenotypes other than E2/2. One subject was apparently homozygous for apo E2 by IEF, but heterozygous for ϵ3/2 by RI. Sequencing of the apo ϵ gene disclosed a hitherto undescribed point mutation (TG G → TG A ) at the third position of the codon for amino acid 20 (Trp), introducing a premature termination codon. This is the first study demonstrating that in the German population type III HLP is mainly associated with homozygosity for apo E2 (Arg 112 → Cys, Arg 158 → Cys) and that discrepancies between apo ϵ genotype and apo E phenotype are rare in this genetic condition. Hum Mutat 11:417–423, 1998. © 1998 Wiley‐Liss, Inc.