Molecular basis for apo A-IV polymorphisms.
Apolipoprotein (apo) A-IV is involved in the metabolism of triglyceride-rich lipoproteins and high-density lipoproteins and may thus play an important role in lipid metabolism, although the precise physiological function of apo A-IV is unknown. Structural and functional alterations of apolipoproteins, caused by a variety of mutations, have been shown to influence lipoprotein metabolism in several ways. Genetic studies are consistent with a single locus for apo A-IV with two main codominant alleles A-IV1 and A-IV2. The basis behind some of these electrophoretic variants has been determined on a molecular level by the aid of the polymerase chain reaction and sequencing of the amplified DNA. For instance, apo A-IV1 and apo A-IV2 alleles are explained by glutamine for histidine change of amino acid 360. Furthermore, several polymorphisms not leading to charge differences have been characterized. The genetic variability of apo A-IV may be of help in elucidating the functional role of apo A-IV in lipoprotein metabolism. In our study, the frequencies of the alleles due to Gln360-->His and Thr347-->Ser substitutions in a Finnish population sample were similar to those reported from other populations. In addition we have identified a novel genetic polymorphism of apo A-IV, Asn127-->Ser. In the Finnish population the asparagine for serine change of amino acid 127 was the most common apo A-IV polymorphism. There are no reports from other populations concerning this polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS)
Tenkanen
H
H
National Public Health Institute, Helsinki, Finland.
Ehnholm
C
C
D000483:Alleles; D001054:Apolipoproteins A / Q000032:analysis / Q000235:genetics*; D003327:Coronary Disease / Q000097:blood / Q000235:genetics; D004586:Electrophoresis; D005260:Female; D005796:Genes / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008297:Male; D011110:Polymorphism, Genetic
D001054:Apolipoproteins A; D008055:Lipids; D008074:Lipoproteins; C022205:apolipoprotein A-IV