Structure, evolution, and polymorphisms of the human apolipoprotein A4 gene (APOA4)

Area of Science:

• Human genetics
• Molecular evolution
• Lipid metabolism

Background:

• Apolipoproteins A1 (APOA1), C3 (APOC3), and A4 (APOA4) are crucial for plasma lipid transport.
• These genes are located on human chromosome 11, suggesting a shared evolutionary origin.

Purpose of the Study:

• To isolate and characterize the human apolipoprotein A4 (APOA4) gene.
• To compare the gene structure of APOA4 with APOA1 and APOC3.
• To investigate the evolutionary relationship between these genes and their genetic polymorphisms.

Main Methods:

• Gene isolation and characterization of the human APOA4 gene.
• Intron-exon structure analysis and comparison with APOA1 and APOC3.
• Restriction endonuclease mapping and haplotype analysis of polymorphic sites.
• DNA analysis of a patient with APOA1-APOC3 deficiency.

Main Results:

• The APOA4 gene contains two introns, differing from the three introns in APOA1 and APOC3 genes.
• An intron present in the 5' noncoding region of APOA1 and APOC3 is absent in APOA4.
• Polymorphic restriction sites (Xba I) near the APOA4 gene show no significant nonrandom association.
• The APOA4 gene structure is normal in a patient with combined APOA1-APOC3 deficiency and premature coronary artery disease.

Conclusions:

• The APOA4 gene likely evolved from a common ancestor with APOA1 and APOC3, having lost an ancestral intron.
• The identified polymorphisms in the APOA4 region are inherited independently.
• The APOA4 gene is not structurally altered in individuals with APOA1-APOC3 deficiency and related cardiovascular issues.