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.
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.
Leren
T P
TP
Department of Medical Genetics, Ullevaal University Hospital, Oslo, Norway.
Bakken
K S
KS
Daum
U
U
Ose
L
L
Berg
K
K
Assmann
G
G
von Eckardstein
A
A
D000328:Adult; D016632:Apolipoprotein A-I / Q000031:analogs & derivatives / Q000235:genetics*; D001053:Apolipoproteins / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D006579:Heterozygote; D006801:Humans; D008055:Lipids / Q000097:blood; D017270:Lipoprotein(a) / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D010375:Pedigree; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D011498:Protein Precursors / Q000097:blood*; D012016:Reference Values
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D008076:Cholesterol, HDL; D008055:Lipids; D017270:Lipoprotein(a); D011498:Protein Precursors; C054949:apolipoprotein II; C078260:lipoprotein A-I; D007862:Phosphatidylcholine-Sterol O-Acyltransferase