A PENTANUCLEOTIDE REPEAT POLYMORPHISM IN THE 5' CONTROL REGION OF THEAPOLIPOPROTEIN(A) GENE IS ASSOCIATED WITH LIPOPROTEIN(A) PLASMA-CONCENTRATIONS IN CAUCASIANS

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 trans cribed kringle4 repeats (K4-VNTR) in the gene explains a large fractio n of this variation, whereas the rest is presently unexplained. We her e have analyzed the effect of the K4-VNTR and of a pentanucleotide rep eat polymorphism (TTTTA)n (n = 6-11) in the 5' control region of the a po(a) gene on plasma Lp(a) levels in unrelated healthy Tyroleans (n = 130), Banes (n = 154), and Black South Africans (n = 112). The K4-VNTR had a significant effect on plasma Lp(a) levels in Caucasians and exp lained 41 and 45% of the variation in Lp(a) plasma concentration in Ty roleans and Danes, respectively. Both, the pentanucleotide repeat (PNR ) allele Frequencies and their effects on Lp(a) concentrations were he terogeneous among populations. A significant negative correlation betw een the number of pentanucleotide repeats and the plasma Lp(a) concent ration was observed in Tyroleans and Banes. The effect of the 5' PNRP on plasma Lp(a) concentrations was independent from the K4-VNTR and ex plained from 10 to 14% of the variation in Lp(a) concentrations in Cau casians. No significant effect of the PNRP was present in Black Africa ns. This suggests allelic association between PNR alleles and sequence s 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.