Studies of apolipoprotein (a) promoter from subjects with different plasma lipoprotein (a) concentrations

Abstract

Objective High plasma lipoprotein (a) [Lp(a)] level is closely related to coronary heart disease and cerebral thrombosis. The Lp(a) concentration is determined primarily by apolipoprotein (a) [apo(a)] gene and APO(a) mRNA abundance has been found to vary with apo(a) isoform. Our objective is to investigate whether APO(a) promoter activity is related to plasma Lp(a) level. Design and methods The 5′ 1.4 kilobases (kb) promoter region of APO(a) was cloned into plasmid pGL-2 basic that carries luciferase reporter system. The promoter activity was assayed in HepG2 cells. DNA sequence of the promoter was also determined. Results Few nucleotide changes besides the variations at the five polymorphic sites: −1270 (TTTTA repeat), −868 (T repeat), −772 (A/G variation), +93 (C/T variation) and +121 (A/G variation) were observed in these promoters. APO(a) promoter activity differed in subjects with different plasma Lp(a) levels. Conclusion : The sequence variation of APO(a) promoter region may contribute to the variation of its transcription activity.