Heterozygosity for apolipoprotein A-I(R160L)Oslo is associated with low levels of high density lipoprotein cholesterol and HDL-subclass LpA-I/A-II but normal levels of HDL-subclass LpA-I.

Abstract

We studied a Norwegian patient and his family, who presented with low HDL-cholesterol. DNA sequence analysis of the apoA-I gene revealed heterozygosity for a mutation in the apoA-I gene that causes a leucine for arginine replacement at residue 160. Compared to unaffected family members, heterozygous carriers of apoA-1 (R160L)Oslo had 60-70% lower mean levels of HDL-cholesterol, 50-60% lower mean levels of apoA-I and 70-80% lower levels of apoA-II. Moreover, the serum concentration of the apoA-II-containing HDL-subclass LpA-I/A-II was decreased by 70% whereas the concentration of the apoA-II-free HDL-subclass LpA-I did not differ from that in unaffected family members. The decrease of LpA-I/A-II was associated with the lack of large LpA-I/A-II. ApoA-I(R160L)Oslo was present at increased concentrations relative to normal apoA-I in plasma, HDL3, and LpA-I. However, only trace amounts of the variant isoform were detectable in immunopurified LpA-I/A-II. Pre beta1-LpA-I contained normal and variant apoA-I isoforms. We conclude that the failure of apoA-I(R160L)Oslo to form LpA-I/A-II causes low HDL-cholesterol in heterozygous carriers of this apoA-I variant.