Influence of polymorphism Q3405E and mutation A3371V in the apolipoprotein B gene on LDL receptor binding Original Research Article

Familial defective apolipoprotein B (FDB) is due to mutations in the apolipoprotein B (apo B) gene at codon 3500 or 3531 that affect low density lipoprotein (LDL) receptor binding. From sequence analysis the putative receptor binding site was believed originally to be upstream from this at residues 3147–3157 and 3357–3367. Using denaturing gradient gel electrophoresis, mutations were sought in codons 3350–3466. This includes the important positively charged residues 3357–3367. DNA from 928 hyperlipidaemic individuals was studied and two hitherto unknown DNA changes were discovered, one of which resulted in an altered amino acid in the apo B. A known polymorphism Q3405E was also detected at a carrier frequency of 1.4%. Using growth of U937 cells as a measure of binding affinity of LDL to its receptor the newly discovered mutant A3371V permitted the same growth as LDL from normolipidaemic individuals of the U937 cells, however, the LDL from Q3405E individuals permitted only 77% of the normal growth (P=0.009).