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

Abstract

Plasma lipoprotein(a) (Lp(a)) is a quantitative trait associated with atherothrombotic disease in European and Asian populations. Lp(a) concentrations vary widely within and between populations, with Africans exhibiting on average two-to threefold higher Lp(a) levels and a different distribution compared to Europeans. The apo(a) gene locus on chromosome 6q26 -27 (LPA, MIM 152200) has been identified as the major quantitative trait locus (QTL) for Lp(a) concentrations in Europeans and populations of African descent (North American and South African Blacks) but data on autochthonous Black Africans are lacking. Here, we have analysed Lp(a) plasma concentrations, apo(a) isoforms in plasma and four polymorphisms in the LPA gene in 31 African families with 54 children from Gabon. Weighted midparent -offspring regression estimated a heritability h 2 ¼ 0.76. The correlation of Lp(a) levels associated with LPA alleles identical by descent (IBD) resulted in a heritability estimate of 0.801. Our data demonstrate that Lp(a) concentrations are highly heritable in a Central African population without admixture and high Lp(a) (median 43 mg/dl). LPA is the major QTL, explaining most or all of the heritability of Lp(a) in this population.

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.…”

Structure, function, and genetics of lipoprotein (a)

“…As mentioned before, LPA is the major gene controlling the Lp(a) trait and explains 70-90% of the variance in Lp(a) levels (24,26). However, the KIV-2 CNV alone explains only a considerably smaller fraction (19-77%) of the variation in Lp(a) concentrations depending on the population and methods used (35,36,173,177).…”

“…In general, it is weaker in populations of African descent than in Asians or Europeans (24,35,36,170,171), explaining 61-69% of the variance in Lp(a) levels in populations of European descent, but only 19-44% in African populations (24,35,36,170,(172)(173)(174). Furthermore, differences in KIV-2 allele frequency distributions alone do not explain the vast differences observed in Lp(a) levels across populations.…”

New Insights into the Assembly and Metabolism of ApoB-Containing Lipoproteins from in vivo Kinetic Studies: Results on Healthy Subjects and Patients with Chronic Kidney Disease

“…Among individuals, Lp(a) plasma concentrations vary more than 1000-fold, ranging from less than 0.1 mg/dl to more than 300 mg/dl. Depending on the investigated population and the used genetic approach, it has been shown that between 30% and 90% of this variation in plasma concentrations of Lp(a) is determined by the apo(a) gene locus, encoding proteins from <300 to >800 kDa [16][17][18]. Apo(a) size is negatively correlated with Lp(a) concentrations, such that low-molecular-weight (LMW) apo(a) isoforms express on average high Lp(a) plasma concentrations, while high-molecular-weight (HMW) isoforms are usually associated with lower concentrations (reviewed in reference [15]).…”