Increased Intestinal Cholesterol Absorption in Autosomal Dominant Hypercholesterolemia and No Mutations in the Low-Density Lipoprotein Receptor or

Context: Autosomal dominant hypercholesterolemia (ADH) is fre-quently caused by functionalmutations in the low-density lipoprotein receptor (LDLR) or apolipoprotein B-100 (APOB) genes, but approx-imately 40 % of ADH subjects disclose no such molecular defects, possibly pointing to alternative genetic mechanisms. Objective: Our objective was to test the hypothesis that increased intestinal cholesterol absorption might play a role in the lipid abnor-malities of subjects with ADH without identified genetic defects. Design and Setting: This is a cross-sectional study of consecutive subjects with primary hyperlipidemia identified during an 18-month period in two lipid clinics. Study Subjects: A total of 52 subjects with a clinical diagnosis of ADH were examined for molecular defects in LDLR and APOB. No APOB defects were found. FunctionalLDLRmutations occurred in 31 (60%) subjects, who received a diagnosis of familial hypercholester-olemia (FH). Those for whom no mutations could be identified were labeled as non-FH ADH. In addition, 38 subjects with familial com-bined hyperlipidemia (FCH) and 45 normolipidemic control subjects were studied. Interventions: Interventions were diagnostic. Main Outcome Measures: Serum noncholesterol sterols were used as markers for the efficiency of intestinal cholesterol absorption. Results: Adjusted campesterol to cholesterol ratios increased in the order non-FHADHmore thanFHmore than controlsmore thanFCH, with mean values (95 % confidence interval) in 102 mmol/mol choles