Polymorphisms in the apolipoprotein(a) gene, plasma Lp(a) and cardiovascular risk

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Authors

BENEŠ Petr

Year of publication 2003
Type Article in Periodical
Magazine / Source HeartDrug
MU Faculty or unit

Faculty of Science

Citation
Field Genetics and molecular biology
Keywords Apolipoprotein(a); lipoprotein(a); genetic polymorphism; cardiovascular risk
Description Increased plasma concentration of lipoprotein(a) [Lp(a)] represents an established risk factor for coronary artery disease. Plasma Lp(a) level is relatively stable during life and it is more than 90% genetically determined by the apolipoprotein(a) [apo(a)] gene. Numerous polymorphisms have been identified in the apo(a) gene. The extreme apo(a) protein size polymorphism, based on variable number of so-called kringle IV type 2 repeats (KIV-2), accounts for a large portion of variability of plasma Lp(a) levels. Moreover, it has been shown that several other apo(a) sequence changes, both in the coding and regulatory sequences, influence plasma Lp(a) levels and/or Lp(a) prothrombogenic properties. Associations between some of them and the increased risk of coronary artery disease have also been reported. However, the existence of strong linkage disequilibria in the apo(a) locus represents a serious problem to identify a real effect of single polymorphism on Lp(a) phenotype. Large and complex association and family studies in different populations, together with in vitro expression and functional studies, should clarify the importance of so far identified positive apo(a) polymorphism - plasma Lp(a) associations in the future. In addition, standardization of measurement of Lp(a) is necessary to allow a comparability of results obtained with different immunoassays.
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