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Elevated plasma lipoprotein(a) [Lp(a)] level has been established as an independent risk factor for atherosclerosis and coronary heart disease. Considerable ethnic group differences in the distribution of plasma Lp(a) levels have raised public health concerns. Recently, we have reported that Samoans have the lowest plasma Lp(a) levels of any population group. In the present investigation, we report the contribution of two apolipoprotein(a) (APOA) polymorphisms, the kringle 4 type 2 (K4) repeat and the pentanucleotide repeat (PNR), in affecting plasma Lp(a) levels in an American Samoan sample (n ~ 309). The K4 repeats ranged in size from 15 to 40. The common aneles contained repeats ranging from 26 to 36 with allele frequencies between 5.5% to 9.7%, and these accounted for 82% of an alleles. An inverse relationship between K4 repeat nnmber and plasma Lp(a) level was observed for single-banded (r ~ - 0.59, P ~ 0.0001) and double-banded phenotypes (r ~ - 0.50, p ~ 0.0001). This polymorphism explained 60% of the variation in plasma Lp(a) level in American Samoans. For the PNR polymorphism, five different repeat aneles and eight different genotypes were identified; the most common anele was eight repeats. The *8 PNR anele was associated with a wide range of K4 repeats, the *9 PNR allele with larger K4 repeats (25-40), and the *10 PNR with smaller K4 repeats (15-24). Analysis of variance (ANOV A) revealed that the PNR polymorphism accounts for 2.1 % of the variability in plasma Lp(a) levels in this sample, when the K4 repeat polymorphism was taken into account. Our data show that common polymorphisms in the APOA gene are major detenninants of plasma Lp(a) variation in American Samoans.