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A pentanucleotide repeat polymorphism in the 5' control region of the apolipoprotein(a) gene is associated with lipoprotein(a) plasma concentrations in Caucasians.
M Trommsdorff, S Köchl, A Lingenhel, F Kronenberg, R Delport, H Vermaak, L Lemming, I C Klausen, O Faergeman, G Utermann
M Trommsdorff, S Köchl, A Lingenhel, F Kronenberg, R Delport, H Vermaak, L Lemming, I C Klausen, O Faergeman, G Utermann
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Research Article

A pentanucleotide repeat polymorphism in the 5' control region of the apolipoprotein(a) gene is associated with lipoprotein(a) plasma concentrations in Caucasians.

Abstract

The enormous interindividual variation in the plasma concentrations of the atherogenic lipoprotein(a) [Lp(a)] is almost entirely controlled by the apo(a) locus on chromosome 6q26-q27. A variable number of transcribed kringle4 repeats (K4-VNTR) in the gene explains a large fraction of this variation, whereas the rest is presently unexplained. We here have analyzed the effect of the K4-VNTR and of a pentanucleotide repeat polymorphism (TTTTA)n (n = 6-11) in the 5' control region of the apo(a) gene on plasma Lp(a) levels in unrelated healthy Tyroleans (n = 130), Danes (n = 154), and Black South Africans (n = 112). The K4-VNTR had a significant effect on plasma Lp(a) levels in Caucasians and explained 41 and 45% of the variation in Lp(a) plasma concentration in Tyroleans and Danes, respectively. Both, the pentanucleotide repeat (PNR) allele frequencies and their effects on Lp(a) concentrations were heterogeneous among populations. A significant negative correlation between the number of pentanucleotide repeats and the plasma Lp(a) concentration was observed in Tyroleans and Danes. The effect of the 5' PNRP on plasma Lp(a) concentrations was independent from the K4-VNTR and explained from 10 to 14% of the variation in Lp(a) concentrations in Caucasians. No significant effect of the PNRP was present in Black Africans. This suggests allelic association between PNR alleles and sequences affecting Lp(a) levels in Caucasians. Thus, in Caucasians but not in Blacks, concentrations of the atherogenic Lp(a) particle are strongly associated with two repeat polymorphisms in the apo(a) gene.

Authors

M Trommsdorff, S Köchl, A Lingenhel, F Kronenberg, R Delport, H Vermaak, L Lemming, I C Klausen, O Faergeman, G Utermann

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