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Phytosterolemia or Sitosterolemia is a rare autosomal recessive disorder characterized by highly elevated plasma levels of plant sterols and cholesterol as a consequence of hyperabsorption and impaired biliary secretion of sterols. The disease is caused by mutations in two half size ATP-binding cassette transporters, ABCG5 and ABCG8. We have analyzed the genomic sequence of ABCG5 and ABCG8 in five well-characterized patients with Sitosterolemia. In the first patient we found a heterozygous mutation in exon 8 of the ABCG5 gene leading to a premature termination of the protein (Arg408Ter). This German patient is the first European showing a mutation of the ABCG5 gene. In a second patient we found a novel heterozygous mutation in exon 5 of ABCG8 (c.584T>A; Leu195Gln). Both patients were heterozygous for the identified mutation, but no mutation could be identified on the other chromosome. In three further analyzed patients we found mutations in exons 7, 9 and 11 of the ABCG8 gene, respectively, of which two result in a premature termination signal for translation products. One of these patients was compound heterozygous (Trp361Ter and Arg412Ter), the other was homozygous for Trp361Ter. The third patient was homozygous for an amino acid exchange (Gly574Arg). In conclusion this report describes one novel mutation affecting a highly conserved amino acid and two previously identified mutations in the ABCG8 gene. In addition, we identified for the first time a mutation in the ABCG5 gene of a European Sitosterolemia patient., (Copyright 2002 Wiley-Liss, Inc.)

Recent trials on the efficacy of drugs and hormones in lowering cholesterol and correcting lipoprotein profiles are reviewed. Emphasis is placed on the risk-benefit ratio, which determines the clinical value of therapeutic regimens. Whereas 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors have set a standard for treatment of hyperlipidaemia, the role of hormone replacement therapy in postmenopausal women in the prevention of coronary artery disease has more recently become better defined.

Human subjects were infused intraduodenally with either lecithin (150 mg/kg/hr) or safflower oil (100 mg/kg/hr)of similar fatty acid composition, and plasma lipoproteins were studied when constant plasma lipid levels were reached. Both types of fat induced increases of lipoproteins of Sf > 400 (chylomicrons) and Sf 20--400 (VLDL). Lecithin infusions produced increases predominantly in VLDL, whereas infusion of safflower oil induced mainly chylomicrons. Chylomicrons derived from lecithin were generally smaller and had a high phospholipid:triglyceride ratio (mean 0.15) than those produced during safflower oil infusions (mean 0.08). The increases in VLDL from both lipids occurred mainly in larger particles of this density range. This "incremental VLDL" had a lower cholesterol:triglyceride ratio (0.098) than preinfusion VLDL (0.283) and probably represented "small chylomicrons" of gut origin. The differences in lipoproteins resulting from infusion of lecithin and safflower oil in human subjects were not observed in rats; in the latter, lecithin induced large chylomicrons to the same extent as did safflower oil. Lecithin absorption measured over 50- or 100-cm intestinal segments averaged 41%, but was probably greater over the whole of the small intestine. Lecithin infusion unexpectedly was found to decrease markedly the absorption of cholesterol in the upper part of the small intestine.