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Simple precipitation-based method for the screening of type III hyperlipoproteinemia.

Familial type III hyperlipoproteinemia (HLP) is characterized by the accumulation of cholesterol-rich remnants (β-VLDL). The differential diagnosis of type III HLP is clinically important because patients with type III HLP develop premature coronary artery disease (CAD) and peripheral atherosclerosis and because type III HLP responds well to dietary treatment and fibric acid derivatives(1)(2). Pathogenetically, type III HLP is related to dysfunctional isoforms of apolipoprotein (apo) E. At the APOE gene locus, three common alleles exist, designated e2, e3, and e4 (3)(4)(5). apoE2 is defective in its binding to lipoprotein receptors(6)(7). Because of the impaired catabolism of chylomicron and VLDL remnants, individuals homozygous for apoE2 reveal detectable amounts of β-VLDL in their plasma. β-VLDLs are atypical lipoproteins with a density <1.006 kg/L and β-mobility on agarose gel electrophoresis. Compared with normal VLDL, β-VLDLs are cholesterol-enriched; compared with normal LDL, they are relatively enriched in triglycerides. More than 90% of patients with type III HLP are homozygous for apoE2, but only ∼1 in 20 individuals carrying the E2/2 phenotype finally develops type III HLP (8). Those homozygous carriers of apoE2 having small amounts of β-VLDL in their plasma not sufficient to produce overt hyperlipidemia have been classified as suffering from normolipidemic dysbetalipoproteinemia. The term type III HLP, in contrast, is applied to hyperlipemic individuals only.

Clinical characteristics such as palmar, tendon, and/or tubero-eruptive xanthomas do not occur in all individuals with type III HLP. To establish biochemically the diagnosis of type III HLP, the following criteria have been applied in this study: (a) presence of increased cholesterol and triglycerides at 2500 mg/L or more, (b) an increased ratio of VLDL-cholesterol (VLDL-C) to VLDL-triglycerides (VLDL-TG; >0.4), and (c) an increased ratio of VLDL-C to total triglycerides (>0.3) (9)(10)(11). …