The relationship among apolipoprotein(a) polymorphisms, the low-density lipoprotein receptor-related protein, and the very low density lipoprotein receptor genes, and plasma lipoprotein(A) concentration in the Czech population.
Increased plasma concentration of lipoprotein(a) [Lp(a)] is an established independent risk factor for coronary artery disease (CAD), which is strongly genetically determined. This study was designed to investigate the relationship between the K-IV and (TTTTA)n apolipoprotein(a) [apo(a), protein; APOA, gene] polymorphisms, as well as the C766T low-density lipoprotein receptor-related protein (LRP) and the (CGG)n very low density lipoprotein receptor (VLDLR) polymorphisms on the one hand, and plasma Lp(a) levels in Czech subjects who underwent coronary angiography on the other hand. The lengths of the alleles of the APOA K-IV and (TTTTA)n polymorphisms were strongly inversely correlated with plasma Lp(a) levels in univariate analysis (r = -0.41, p < 10(-4) and r = -0.20, p < 0.01, respectively). Multivariate analysis revealed significant associations between the APOA polymorphisms studied and plasma Lp(a) levels in subjects expressing only one APOA K-IV allele (p < 10(-6) for K-IV and p < 0.001 for TTTTA). In subjects expressing both APOA K-IV alleles, the multivariate analysis revealed that only the APOA K-IV alleles were inversely correlated with plasma Lp(a) levels (p < 0.001). Associations between both the LRP and VLDLR gene polymorphisms and plasma Lp(a) levels were only of borderline significance (p < 0.06 and p < 0.07, respectively) and were not confirmed in multivariate analysis. In conclusion, both APOA length polymorphisms significantly influenced plasma Lp(a) concentration in the Czech population studied, and this circumstance could explain the association in this population observed earlier between APOA (TTTTA)n polymorphism and CAD (Benes et al. 2000). Only a minor role in the regulation of plasma Lp(a) levels is suggested for the C766T LRP and the (CGG)n VLDLR polymorphisms.
Benes
Petr
P
Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Muzík
Jan
J
Benedík
Jaroslav
J
Znojil
Vladimír
V
Vácha
Jirí
J
D000483:Alleles; D000704:Analysis of Variance; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics*; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D018153:Czech Republic / Q000453:epidemiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016014:Linear Models; D017270:Lipoprotein(a) / Q000097:blood*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011973:Receptors, LDL / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D018709:Statistics, Nonparametric
D001054:Apolipoproteins A; D017270:Lipoprotein(a); D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011973:Receptors, LDL