Perez-Mendez_2006_Clin.Chim.Acta_368_149

BACKGROUND: Lipoprotein lipase (LPL) deficiency has been suggested as a cause of low HDL-cholesterol (HDL-C) plasma levels, by a mechanism that involves an enhanced catabolism of HDL apolipoprotein (apo) AI. To verify the role of 2 different LPL gene mutations on HDL metabolism, we studied the in vivo turnover of the apo AI and apo AII in heterozygous carriers of LPL deficiency.
METHODS: Apo AI and AII kinetics were studied by a 10-h primed constant infusion of 5,5,5-2H3-leucine approach in 2 carriers, 1 man (patient 1) and 1 woman (patient 2), and 5 control subjects. The rates of HDL apolipoproteins production (PR) and catabolism (FCR) were estimated using a one-compartment model-based analysis.
RESULTS: Both carriers had low HDL-C plasma levels and only patient 1 was hypertriglyceridemic. VLDL apo B was 4-times slower in patient 1 as compared to patient 2. The FCRs of apo AI in both carriers was within the range of the controls (0.200, 0.221 and 0.211+/-0.051 day(-1), respectively). Apo AII FCR in patient 1 was about 20% lower than the mean of the control group whereas being normal in patient 2. Apo AI PR in patient 1 (9.20 mg kg(-1) day(-1)) was below the lowest value in controls (range, 10.52-13.24 mg kg(-1) day(-1)) whereas in patient 2 it was normal. Apo AII PR in both patients was similar to controls. CONCLUSION: The heterozygous carriers of 2 different mutations in the LPL gene had different VLDL apo B FCR, and from normal to slightly low HDL apolipoprotein FCR and PR. These results disagree with the putative enhanced apo AI FCR in LPL deficient patients and suggest the need to reconsider the effects of LPL activity on HDL metabolism.