The apo(a) is of great interest from both genetic and medical points of view in that it exhibits a high genetic polymorphism associated with variation in plasma Lp(a) levels, so high that levels are an independent risk factor for premature atherosclerosis [2]. Since apo(a) exhibits a size polymorphism, SDS-PAGE is a suitable method for the genetic analysis of the apo(a) polymorphism [14].

      We used the 3-15% gradient SDS-PAGE followed by immunoblotting for analysis of apo(a) size polymorphisms. This method resolved five allelic isoforms (B, S1, S3, S4, >S4) in plasma samples from 180 healthy Macedonian blood donors and detected at least one apo(a) isoform in 95% of these individuals. Using SDS-PAGE Uterman et al. [14], separated six isoforms of apo(a) among 441 subjects, while Marcovina et al. [29] reported 34 different apo(a) isoforms among 1507 subjects separated with SDS-agarose gel electrophoresis.

      The Mr of the apo(a) isoforms we observed ranged from 417,000-785,000. This is in agreement with the data of Gaubatz et al. [30], who resolved 11 apo(a) isoforms using SDS-PAGE with Mr from 419,000 to 838,000.

      Based on family studies, Utermann et al. [14] suggested that apo(a) isoforms are specified by alleles at the apo(a) locus and are inherited in a codominant fashion. They also postulated the existence of a null allele to account for individuals with no detectable apo(a). An apo(a) allele that produces no detectable circulating apo(a) has also been reported by Boerwinkle et al. [19].

      Our data indicate that each apo(a) isoform we de­tected by our method was specified by a corresponding allele at the apo(a) locus, and that the observed frequency distribution of apo(a) phenotypes in the population fit the expectations of the Hardy-Weinberg equilibrium. The distribution of alleles in our subjects was skewed towards alleles encoding large apo(a) isoforms. The frequency distribution pattern of the apo(a) isoform alleles we found is similar to that reported by Lackner et al. [31]. This suggests that the frequency distributions of the apo(a) alleles may be similar among different populations.

      In agreement with the suggestions of Utermann et al. [14] and Gaubatz et al. [30], we observed an inverse correlation (r = –0.3477, p <0.001) between the Mr of the apo(a) isoform and the respective plasma Lp(a) concentration. As proposed by Utermann et al. [14], highly skewed distribution of plasma Lp(a) levels can be accounted for by high frequencies of alleles encoding large apo(a) iso­forms and a null allele.