Articles |
From the Department of Medicine, Division of Cardiology, Helsinki University Central Hospital (M.I., T.H., M.J.T.), the Department of Clinical Chemistry, University of Helsinki (A.P.), the National Public Health Institute (P.P., J.K.H.), Helsinki, Finland, and the Blood Transfusion Service of the Swiss Red Cross, Bern, Switzerland (R.B.).
Correspondence to Marja Ilmonen, MD, Helsinki University Central Hospital, Department of Medicine, Laboratory of Biochemistry L222, Haartmaninkatu 4, FIN-00290 Helsinki, Finland.
Abstract In previous studies, apoB polymorphisms have
been shown to modify serum lipid responses to changes in dietary fat
intake. The functionally important apoB DNA change or changes
underlying these effects have, however, remained unknown. Using a
single-strand conformation polymorphism analysisbased
screening method, we identified two previously unreported apoB
polymorphisms located close to each other in the 5' region of apoB
gene exon 26. This DNA segment corresponds to the binding site of
monoclonal anti-apoB antibody D7.2. The two A
G changes at apoB cDNA
nucleotides 5869 and 5896 produced an Asn
Ser change at
amino acid 1887 and a His
Arg change at amino acid 1896. In the
Finnish population, allele frequencies of the rare alleles of
the apoB 1887 (Asn
Ser) and apoB 1896 (His
Arg) polymorphisms
were .02 and .11, respectively. Both polymorphisms were shown to
have an independent effect on the binding affinity of LDL with
monoclonal antibody D7.2. The effect of these polymorphisms on
serum lipid levels and responses to changes in dietary fat intake in
102 healthy free-living subjects was assessed. The apoB 1896 Arg
allele was associated with a higher serum LDL
cholesterol level during a low-fat,
low-cholesterol diet in men.
Key Words: apoB gene polymorphisms apoB antigenic polymorphisms low-fat, low-cholesterol diet
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