Genetic variants of ApoE account for variability of plasma low-density lipoprotein and apolipoprotein B levels in FHBL

Pin Yue, William L. Isley, William S. Harris, Stefan Rosipal, Carl D. Akin, Gustav Schonfeld

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

We report two novel APOB mutations causing short apolipoprotein B (apoB) truncations undetectable in plasma and familial hypobetalipoproteinemia (FHBL). In Family 56, a 5 bp deletion in APOB exon 7 (870_874del5) causes a frame shift, converting tyrosine to a stop codon (Y220X) and producing an apoB-5 truncation. In Family 59, a point mutation (1941G>T) in APOB exon 13 converts glutamic acid to stop codon (E578X), specifying apoB-13. A recurrent mutation in exon 26 (4432delT) produces apoB-30.9 in Family 58. In some members of these families, we observed that plasma low-density lipoprotein (LDL) cholesterol and apoB levels were unusually low even for subjects heterozygous for FHBL. To ascertain whether genetic variations in apolipoprotein E (apoE) would explain some of the variations of apoB and LDL cholesterol levels, apoE genotypes were assessed in affected subjects from a total of eight FHBL families with short apoB truncations. Heterozygous FHBL with the ε3/ε4 genotype had 10-15 mg/dL higher plasma LDL cholesterol and apoB levels compared to subjects with the ε2/ε3 and ε3/ε3 genotypes. The apoE genotype has been reported to account for ∼10% of the variation of LDL cholesterol in the general population. It accounted for 15-60% of the variability of plasma LDL cholesterol or apoB levels in our FHBL subjects. The physiologic bases for the greater effects of apoE in FHBL remain to be determined.

Original languageEnglish (US)
Pages (from-to)107-113
Number of pages7
JournalAtherosclerosis
Volume178
Issue number1
DOIs
StatePublished - Jan 1 2005

Keywords

  • ApoB
  • ApoB truncation
  • Apolipoprotein E
  • FHBL
  • LDL cholesterol

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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