Authors: G Schonfeld X Lin P Yue
Publish Date: 2005/04/07
Volume: 62, Issue: 12, Pages: 1372-
Abstract
Familial hypobetalipoproteinemia FHBL an autosomal dominant disorder is defined as 5th percentile LDLcholesterol or apolipoprotein apo B in the plasma FHBL subjects are generally heterozygous and asymptomatic Three genetic forms exist i premature stop codon specifying mutations of APOB ii FHBL linked to a susceptibility locus on the chromosome 3p21 and iii FHBL linked neither to APOB nor to the chromosome 3p21 In heterozygous apoBdefective FHBL the hepatic VLDL export system is defective because apoB 100 the product of the normal allele is produced at ∼5 of normal rate and truncated apoB is cleared too rapidly The reduced capacity for hepatic triglyceride export increases hepatic fat threefold Indexes of adiposity and insulin action are similar to controls ‘Knockin’ mouse models of apoB truncations resemble human FHBL phenotypes Liver fat in the chromosome 3p21linked FHBL is normal Elucidation of the genetic basis of the nonapoB FHBL could uncover attractive targets for lipidlowering therapy See note added in proof
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