Screening of the 3' two-thirds of the coding area of the apo B gene in Finnish hypercholesterolemic patients report of six new genetic variants.

Hypercholesterolemia clustering in families not explained by either low density lipoprotein (LDL)-receptor mutations producing familial hypercholesterolemia (FH), or the apolipoprotein B (apo B) Arg3500-->Gln mutation with familial defective apo B (FDB), is common in the Finnish population. In search of previously unknown apo B mutations, we screened exons 26 to 29 of the apo B gene in 68 Finnish severely hypercholesterolemic (> or = 8 mmol/l) non-FH, non-FDB patients, using a single-strand conformation polymorphism analysis based screening method. Four rare and two polymorphic previously unreported DNA variations were detected. The rare variants were a three-nucleotide deletion, with the deletion of Asp2186, an A11961-->G change leading to a Thr3918-->Ala change, a T12922-->G change causing a Val4238-->Ala substitution, and a neutral T12935-->C change leading to a new RsaI cutting site. The polymorphic G12937-->C and G13569-->A changes leading to Arg4243-->Thr and Ala4454-->Thr substitutions, respectively, had minor allele frequencies of 0.03 and 0.02. None of these variants seemed to explain the hyperlipidemia in these patients. A major Finnish mutation causing severe hypercholesterolemia is unlikely to exist in the 3' two-thirds of the coding area of the apo B gene.