FREQUENCY-DISTRIBUTIONS OF APOLIPOPROTEIN(A) KRINGLE-IV REPEAT ALLELES AND THEIR EFFECTS ON LIPOPROTEIN(A) LEVELS IN CAUCASIAN, ASIAN, AND AFRICAN POPULATIONS - THE DISTRIBUTION OF NULL ALLELES IS NONRANDOM

A size polymorphism (K IV VNTR) and largely unknown sequence variation in the apolipoprotein(a) [apo(a)] gene on chromosome 6q26-q27 togethe r determine most of the extreme variation in apo(a) glycoprotein expre ssion and lipoprotein(a) [Lp(a)] plasma concentration in Caucasians. W e have determined Lp(a) plasma concentrations, the number of kringle I V (K IV) repeats in the apo(a) gene and the expression of the apo(a) g lycoprotein in four ethnic groups (Khoi San, South African Blacks, Hon g Kong Chinese and Caucasians from the Tyrol, total n = 788). The dist ributions of Lp(a) concentrations, the frequencies of expressed and no n-expressed apo(a) K IV alleles, and the impact of the size polymorphi sm on Lp(a) concentrations were all heterogeneous across populations. In contrast, the effect of the K IV repeat alleles appeared homogeneou s. Lp(a) concentrations were higher in Africans and Chinese than in Ca ucasians, but this was not explained by differences in K IV repeat all ele frequencies among populations. Lp(a) concentrations were highest i n Khoi San, suggesting that high Lp(a) is an old African trait. When e xpressed as Spearman rank correlations the impact of the size polymorp hism was smallest in African Blacks (R = -0.386) and largest in the Ch inese (R = -0.692). In all four populations, the distribution of non-e xpressed apo(a) alleles was non-random. Rather they were significantly associated with distinct size alleles and overall positively with hig h K IV repeat numbers. The negative correlation of K IV repeat length with Lp(a) concentration was nonlinear in Khoi San and the average apo (a)-size-allele-associated Lp(a) concentrations were markedly differen t between all populations. We conclude that besides the apo(a) size va riation, other factors affect Lp(a) concentrations to different degree s in the study populations. Most likely, this is sequence variation in apo(a) which is not the same in the different ethnic groups.