title: 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.
abstract: 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.
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Finland. marja.ilmonen@hyks.mailnet.fi
authors.forename: M
authors.initials: M
authors.lastname: Ilmonen
authors.forename: T
authors.initials: T
authors.lastname: Ebeling
authors.forename: J
authors.initials: J
authors.lastname: Viikari
authors.forename: J P
authors.initials: JP
authors.lastname: Ojala
authors.forename: M J
authors.initials: MJ
authors.lastname: Tikkanen
mesh_terms: D001055:Apolipoproteins B / Q000235:genetics*; D001483:Base Sequence; D005091:Exons; D005387:Finland; D005787:Gene Frequency; D005815:Genetic Code; D005820:Genetic Testing; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D008055:Lipids / Q000097:blood; D010375:Pedigree; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D001055:Apolipoproteins B; D008055:Lipids