Denaturing Gradient Gel Electrophoretic Analysis of Codons 3456–3553 of the Apolipoprotein-B Gene in 106 Type 11a Hyperlipoproteinaemic Individuals

Familial defective apolipoprotein B-100 (FDB) is commonly attributable to mutation of glutamine to arginine in codon 3500 of the apolipoprotein B (APOB) gene. APOB, the protein component of low-density lipoprotein (LDL) acts as the ligand for the LDL receptor (LDLR), mediating the clearance of LDL from plasma. This mutation causes hypercholesterolaemia and consequent coronary artery disease phenotypically similar to familial hypercholesterolaemia (FH) attributable to LDLR gene defects. APOB gene mutation R3500Q is prevalent in Western Europe, attributable to a single founder mutation, and occurring at up to one in 1000 in the general population and 1%-2% in apparent FH collections. Many studies applying direct assay of patient groups for R3500Q have been undertaken, but there are indications that other ligand defects exist, R3531C and R3500W having been described. Different regions or countries may display different mutational spectra which can be instructive for research and useful for establishing genetic diagnostic assays. Codon region 3456-3553 of the APOB gene contains the mutations so far identified, and therefore is a strong candidate for a functional role in receptor binding. We have applied denaturing gradient gel electrophoresis (DGGE), a sensitive de novo mutation scanning technique, to this region in 106 apparent FH index cases from the South of England.