Genetic variation of apolipoprotein B can produce both low and high levels of apoB-containing lipoproteins in plasma.

The polymorphic markers of the apolipoprotein B (apoB) gene include restriction fragment length polymorphisms (RFLPs) scattered along the length of the gene, an insertion/deletion (I/D) polymorphism at the 5' and variable numbers of tandem repeats (VNTRs) at the 3' untranslated ends. The Xbal and I/D polymorphisms which do not affect apoB structure, produce modest effects on fasting and postprandial lipids and on responsiveness to dietary lipids, but the effects are population, age and gender-dependent. Much larger effects on fasting lipid levels are produced by structural mutations of the apoB gene. The apoB 3500 mutation affecting the low density lipoprotein (LDL) receptor recognition region of apoB-100, is one of the causes of the autosomal codominant familial hypercholesterolemia phenotype, characterized by fasting LDL elevations and atherosclerosis. Neither fasting nor postprandial hypertriglyceridemia are consistently present. Some forms of familial hypobetalipoproteinemia (FHBL) are genetically linked to various truncation-producing mutations of the gene. To date approximately 30 deletion, insertion or non-sense mutations have been identified resulting in apoB truncations ranging in size from apoB-9 to apoB-89. FHBL segregates as an autosomal dominant trait. Heterozygotes have less than a 5th to 10th percentile levels while compound heterozygotes and true homozygotes have much less than 5th percentile levels of total and LDL cholesterol. Heterozygotes have no symptoms traceable to the gene defect. Alterations in the distributions of apoB truncations among the lipoproteins in plasma and in the metabolism of the lipoproteins containing apoB-truncations depend on the lengths of the truncations.