The Number of Identical Kringle IV Repeats in Apolipoprotein(a) Affects Its Processing and Secretion by HepG2 Cells

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

“…Consequently, this association of the rs3798220 variant allele with Lp(a) can be explained by its linkage with KIV CNV size [12,13]. This constitutes a strong argument against the proposition that this variant itself has a causal effect on Lp(a) concentrations.…”

“…Individual Lp(a) levels range from <0.1mg/dl to >200mg/dl. The KIV-2 CNV size is inversely correlated with Lp(a) concentrations in a causal manner, as longer apo(a) isoforms degrade at a higher rate in the hepatocytes prior to secretion [12,13]. However, even same-sized apo(a) isoforms vary in their associated Lp(a) levels between individuals [14], and, on average, between populations [15,16].…”

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

“…Though our present data do not formally exclude the possibility that none of the genetic variance in Lp(a) levels in Africans is explained by the apo(a) locus this is excluded by population genetic studies 16,18 and cell culture experiments. 51 Large population studies based on apo(a) genotyping have shown that variation in the number of Kringle IV repeats in the apo(a) gene explains about 38% of the total phenotypic variance in Blacks and Khoi San. 16 In the present study 34% of the phenotypic variance was attributable to the apo(a) locus.…”

Lipoprotein (a) – An Overview

“…The number of kringle IV type 2 structure repeats results in a large number of different sized isoforms of apo-a and correlates inversely with the plasma concentration of Lp(a) [16]. Although the exact mechanism responsible for this inverse correlation has not been elucidated so far an isoform dependent retention and degradation in the endoplasmatic reticulum has been implicated [17].…”