Demonstration of Physical Linkage between the Promoter Region and the Polymorphic Kringle IV Domain in the Apo(a) Gene by Pulsed-Field Gel Electrophoresis

• Published in: Genomics (San Diego, Calif.) Vol. 17; no. 1; pp. 260 - 262
• Main Authors: Kraft, H.G., Malgaretti, N., Köchl, S., Acquati, F., Utermann, G., Taramelli, R.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.07.1993; Elsevier
• Subjects: 5'-terminus; 550400 - Genetics; Alleles; apolipoprotein (a); APOLIPOPROTEINS; Apolipoproteins - genetics; Apoprotein(a); BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; Electrophoresis, Gel, Pulsed-Field; Fundamental and applied biological sciences. Psychology; GENES; Genes. Genome; Genetic Linkage; Humans; Kringles - genetics; linkage analysis; LIPIDS; Lipoprotein(a); LIPOPROTEINS; man; Molecular and cellular biology; Molecular genetics; MOLECULAR STRUCTURE; ORGANIC COMPOUNDS; Promoter Regions, Genetic - genetics; promoters; PROTEINS; pulsed-field gel electrophoresis; repeated sequence; Human; Apolipoprotein A; Domain structure; Transcription promoter; Chromosome DNA; Gene organization; Polymorphism
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1993.1318

Apolipoprotein(a) is a large glycoprotein that together with a low-density lipoprotein (LDL) particle forms lipoprotein(a) or Lp(a). Lp(a) is a quantitative genetic trait in human plasma. High concentrations of Lp(a) are a genetic risk factor for premature CHD and stroke. Knowledge of apo(a) gene structure and understanding the regulation of Lp(a) plasma levels may therefore be of practical importance. To demonstrate physical linkage of the 5' apo(a) promoter region with the kringle IV repeat region in genomic DNA, we have capitalized from the size variation in the apo(a) gene. Here we demonstrate that the 5' promoter-linked sequence is on a polymorphic DNA fragment that also contains the variable number of kringle IV repeats. The availability of the 5' end of the apo(a) gene will allow detection of potential heterogeneity in this region of the apo(a) gene which might be responsible for the residual unexplained variability of Lp(a) plasma levels. Recently Wade et al. strengthened this hypothesis by reporting differences in the activities of the apo(a) promoters between two individuals with very different Lp(a) levels.