DECREASED RESISTANCE AGAINST IN-VITRO OXIDATION OF LDL FROM PATIENTS WITH FAMILIAL DEFECTIVE APOLIPOPROTEIN B-100

Familial defective apolipoprotein B-100 (FDB) is caused by a mutation in the receptor-binding region of apolipoprotein B-100, the structural protein of the low-density lipoprotein (LDL) particle. We studied the effect of this mutation on the composition and susceptibility to oxid ative modification of LDL in patients with FDB. Twenty Dutch carriers of the mutation identified in a family study were matched with 20 unaf fected siblings of similar age and sex. The mean concentration of LDL cholesterol was 5.19+/-0.94 versus 2.9+/-0.5 mmol/L in control subject s (P<.0001). Measurement of LDL oxidizability in vitro by continuously monitoring conjugated-diene absorbance showed that LDL from FDB patie nts was significantly less resistant against oxidation (lag time, 90+/ -22 minutes versus 108+/-21 minutes; P<.05); furthermore, the maximal rate of diene production and total diene production were also signific antly increased. Analysis of the chemical composition revealed an incr eased relative content of cholesteryl esters and reduced content of pr otein in the LDL of FDB patients (cholesterol-to-protein ratio, 1.54+/ -0.24 versus 1.25+/-0.23; P<.01). The relative amount of arachidonic a cid in LDL was increased and that of stearic acid was decreased. The v itamin E (alpha-tocopherol) content per gram of LDL protein was simila r to that in control subjects. The relative amount of cholesteryl este rs and protein in LDL as well as the fatty acid composition were signi ficantly correlated with LDL oxidizability. Thus, compositional factor s in LDL resulting in increased susceptibility to oxidative modificati on may contribute to the increased risk of premature vascular disease in FDB. (Arterioscler Thromb. 1993;14:489-493.)