Variations in the apolipoprotein AI-CIII-AIV gene region and in lecithin:cholesterol acyltransferase concentration are determinants of plasma cholesterol concentrations.
We have examined the effects of variation in the region of the apolipoprotein (apo) AI-CII-AIV genes, and in plasma lecithin: cholesterol acyltransferase (LCAT) concentration, on plasma cholesterol concentration in 109 unrelated men aged 52-67 yrs. Restriction fragment length polymorphisms (RFLPs) were detected using the restriction enzymes XmnI, PstI and SstI and individuals were divided into groups using information from all three RFLPs in conjunction. Mean plasma concentrations of both total cholesterol and estimated low density lipoprotein-cholesterol differed significantly (P less than 0.0125) among groups of men with different genotypes. Thus, variation in this gene region may be one of the polygenetic factors involved in determining cholesterol levels in the normal population. In the same subjects, plasma cholesterol was also positively correlated with plasma LCAT concentration (r = 0.55, P less than 0.001), due mainly to an increase in the cholesteryl ester content of apo B-containing lipoproteins with increasing LCAT concentration. Since apolipoproteins AI, CIII and AIV have each been shown to modify the activity of LCAT in vitro, the associations of the RFLPs with plasma cholesterol concentration may reflect changes in LCAT activity secondary to qualitative or quantitative changes in one or more of these apolipoproteins.
D000368:Aged; D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A / Q000235:genetics*; D001056:Apolipoproteins C / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D008875:Middle Aged; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood*; D012150:Polymorphism, Restriction Fragment Length
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D008078:Cholesterol, LDL; C022205:apolipoprotein A-IV; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase