Journal of Lipid Research, Vol 38, 121-131, Copyright © 1997 by Lipid Research, Inc.

ARTICLES

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

TP Leren, KS Bakken, U Daum, L Ose, K Berg, G Assmann and A von Eckardstein
Department of Medical Genetics, Ullevaal University Hospital, Oslo, Norway.

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.
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