Genetic control of lipoprotein(a) concentrations is different in Africans and Caucasians

Abstract

Lipoprotein(a) (Lp(a)) represents a quantitative trait in human plasma associated with atherothrombotic disease. Large variation in the distribution of Lp(a) concentrations exists across populations which is at present unexplained. Sib-pair linkage analysis has suggested that the apo(a) gene on chromosome 6q27 is the major determinant of Lp(a) levels in Caucasians. We have here dissected the genetic architecture of the Lp(a) trait in Africans (Khoi San, South African Blacks) and Caucasians (Austrians) by family/sib-pair analysis. Heritability estimates ranged from h2 = 51% in Blacks, h2 = 61% in Khoi San, to h2 = 71% in Caucasians. Analysis by a variance components model also demonstrated that the proportion of the total phenotypic variance explained by genetic factors is smaller in Africans (65%) than in Caucasians (74%). Importantly the sib-pair analysis clearly identified the apo(a) gene as the major locus in Caucasians which explained the total genetic variance. In the African samples the apo(a) gene accounted for only half the genetic variance. Together with previous results from population studies our data indicate that genetic control of Lp(a) levels seems to be distinctly different between Africans and Caucasians. In the former genetic factors distinct from the apo(a) locus and also non-genetic factors may play a major role.