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 h 2 = 51% in Blacks, h 2 = 61% in Khoi San, to h 2 = 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.

Genetics of the Lp(a)/apo(a) system in an autochthonous Black African population from the Gabon

“…However, Scholz et al calculated a heritability of only 0.51 for South African Blacks using weighted midparent -offspring regression (unweighted result: 0.65). 13 These lower values might be considered as indicative of a difference, especially as the results of Scholz et al 13 were obtained by the same laboratory using the same apo(a) detection assay. However, in view of the broad 95% confidence intervals for the heritability estimates (Table 1), differences of heritabilities between the Gabonese and South African Blacks or even Europeans cannot be considered significant.…”

“…13,15,23 A comparative family study of Black South Africans, Khoi-San, and Europeans (Austrians) found that heritabilities of Lp(a) were considerably lower in Africans (h 2 ¼ 0.51) than in Europeans (h 2 ¼ 0.71) and that the LPA locus explained almost 100% of the genetic variance of the Lp(a) trait in the Austrians but less than 50% in the Africans. 13 These data suggested that the contribution of the apo(a) locus on the quantitative Lp(a) trait might be much weaker in Black people and that the higher Lp(a) in Africans might be explained by factors other than the LPA locus. A population study conducted in African Americans and Nigerians indeed suggested a strong gene -environment interaction on Lp(a) in Black people.…”

“…A population study conducted in African Americans and Nigerians indeed suggested a strong gene -environment interaction on Lp(a) in Black people. 23 To date, all family studies of apo(a)/Lp(a) in Black populations 13,15 have been performed in populations which are living in an environment that considerably differs from the situation in most of Africa, and which have a white admixture that may well reach over 20% in African Americans. 24,25 To get a better understanding of the genetic architecture of the LPA trait in Africans, we have performed a family study in an autochthonous Black African population from rural Western Central Africa.…”

Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians

“…Samples came from seven Asian and three African populations, which were all sampled for previous LPA studies [16,[30][31][32]. The African samples consisted of Khoi San of Angolan descent (n=263), sampled in Schmidtsdrift, Republic of South Africa, Gabonese Bantu from the district of Moyen-Ogooué (n=113), Gabon; and Egyptians from Ismailia (n=132), Egypt.…”

“…This assay is highly accurate and has been used in several previous population studies [9,16,[30][31][32]. For the Trobriand Islanders, only DNA samples were available.…”