THE APO(A) GENE IS THE MAJOR DETERMINANT OF VARIATION IN PLASMA LP(A)LEVELS IN AFRICAN-AMERICANS

The distributions of plasma lipoprotein(a), or Lp(a), levels differ si gnificantly among ethnic groups. Individuals of African descent have a two-to threefold higher mean plasma level of Lp(a) than either Caucas ians or Orientals. In Caucasians, variation in the plasma Lp(a) levels has been shown to be largely determined by sequence differences at th e apo(a) locus, but little is known about either the genetic architect ure of plasma Lp(a) levels in Africans or why they have higher levels of plasma Lp(a). In this paper we analyze the plasma Lp(a) levels of 2 57 sibling pairs from 49 independent African American families. The pl asma Lp(a) levels were much more similar in the sibling pairs who inhe rited both apo(a) alleles identical by descent (IBD) (r = .85) than in those that shared one (r = .48) or no (r = .22) parental apo(a) allel es in common. On the basis of these findings, it was estimated that 78 % of the variation in plasma Lp(a) levels in African Americans is attr ibutable to polymorphism at either the apo(a) locus or sequences close ly linked to it. Thus, the apo(a) locus is the major determinant of va riation in plasma Lp(a) levels in African Americans, as well as in Cau casians. No molecular evidence was found for a common ''high-expressin g'' apo(a) allele in the African Americans, We propose that the higher plasma levels of Lp(a) in Africans are likely due to a yet-to-be-iden tified trans-acting factor(s) that causes an increase in the rare of s ecretion of apo(a) or a decrease in its catabolism.