Apolipoprotein(a) gene polymorphisms (TTTTA)n and G/A-914 affect Lp(a) levels in ischemic heart disease patients from Serbia

OBJECTIVES: Lipoprotein(a) (Lp(a)) concentration is determined primarily by the apolipoprotein(a) (apo(a)) gene. The pentanucleotide (TTTTA)n repeat and G/A-914 polymorphisms are in the 5' promoter region of the apo(a) gene. To elucidate whether these polymorphisms affect Lp(a) levels, a total of 211 Serbian adults were investigated. DESIGN: One hundred and eleven patients with ischemic heart disease and 100 healthy controls were genotyped and Lp(a) levels determined. RESULTS: Lp(a) concentrations differed according to the (TTTTA)n genotypes: among those having at least one allele 8, patients had significantly higher Lp(a) values than controls. A decreasing trend of Lp(a) values was associated with the -914A allele in controls but the opposite was true in patients. Patients with genotype TTTTA allele 8/AA-914 had significantly higher Lp(a) values than those without allele 8/AA (p < 0.05). The >8>8/GG genotype was not detected. Significant linkage disequilibrium between (TTTTA)n and G/A-914 polymorphism (p < 0.001) was found. In multivariate regression analysis, the G/A-914 polymorphism significantly (p < 0.05) affected Lp(a) levels in patients, after taking into account the (TTTTA)n polymorphism. CONCLUSION: These results indicate that (TTTTA)n and G/A-914 polymorphisms affect Lp(a) levels in ischemic heart disease as a consequence of the linkage disequlibrium.