Abstract
We studied 22 normal-weight patients with polygenic hypercholesterolemia (PH), of which 11 (two males and nine females) had the apolipoprotein (apo) E3/4 genotype and 11 (one male and 10 females) the E3/3 genotype. The two groups were comparable for age, body mass index, total and low-density lipoprotein (LDL) cholesterol levels. The diagnosis of PH was made on the basis of clinical assessment, the criteria being type IIa hypercholesterolemia without tendon xanthomas and/or family history 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 mevalonic acid (MVA) excretion, an index of whole-body cholesterol synthesis, was evaluated in the steady-state condition while patients were on a low-fat, low-cholesterol diet for at least 3 months. Urinary MVA excretion rates were 2.52 +/- 0.8 micromol/24 h in E3/4 patients, significantly higher (P < .001) than in E3/3 patients (1.38 +/- 0.6 micromol/24 h). This is the first evidence of a higher rate of cholesterogenesis in PH patients carrying the epsilon4 allele versus the epsilon3 allele under a standardized lipid-lowering diet. We conclude tha...Continue Reading
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