APOLIPOPROTEIN-E GENOTYPE AND CHOLESTEROGENESIS IN POLYGENIC HYPERCHOLESTEROLEMIA

We studied 22 normal-weight patients with polygenic hypercholesterolem ia (PH), of which 11 (two males and nine females) had the apolipoprote in (apo) E3/4 genotype and 11 (one male and 10 females) the E3/3 genot ype. The two groups were comparable for age, body mass index, total an d low-density lipoprotein (LDL) cholesterol levels. The diagnosis of P H was made on the basis of clinical assessment, the criteria being typ e Ila hypercholesterolemia without tendon xanthomas and/or family hist ory and clinical criteria indicative of familial hypercholesterolemia and/or familial combined hyperlipidemia. To avoid the influence of the habitual individual diet on cholesterogenesis, daily urinary mevaloni c acid (MVA) excretion, an index of whole-body cholesterol synthesis, was evaluated in the steady-state condition while patients were on a l ow-fat, low-cholesterol diet for at least 3 months. Urinary MVA excret ion rates were 2.52 +/- 0.8 mu mol/24 h in E3/4 patients, significantl y higher (P < .001) than in E3/3 patients (1.38 +/- 0.6 mu mol/24 h). This is the first evidence of a higher rate of cholesterogenesis in PH patients carrying the epsilon 4 allele versus the epsilon 3 allele un der a standardized lipid-lowering diet. We conclude that the higher ra te of cholesterogenesis in PH patients with the epsilon 4 allele might partly explain the interindividual differences in response to treatme nt with cholesterol synthesis inhibitors such as statins. Copyright (C ) 1998 by W.B. Saunders Company.