Increased intestinal cholesterol absorption in autosomal dominant hypercholesterolemia and no mutations in the low-density lipoprotein receptor or apolipoprotein B genes.

Abstract

CONTEXT:

Autosomal dominant hypercholesterolemia (ADH) is frequently caused by functional mutations in the low-density lipoprotein receptor (LDLR) or apolipoprotein B-100 (APOB) genes, but approximately 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 abnormalities 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. Functional LDLR mutations occurred in 31 (60%) subjects, who received a diagnosis of familial hypercholesterolemia (FH). Those for whom no mutations could be identified were labeled as non-FH ADH. In addition, 38 subjects with familial combined 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-FH ADH more than FH more than controls more than FCH, with mean values (95% confidence interval) in 10(2) mmol/mol cholesterol of 505 (424-600), 397 (345-458), 335 (294-382), and 284 (247-328), respectively. Thus, cholesterol absorption was lowest in FCH and highest in non-FH ADH.

CONCLUSIONS:

Increased intestinal cholesterol absorption may partially explain the high cholesterol levels of non-FH ADH subjects. Serum noncholesterol sterols are a useful tool for the differential diagnosis of genetic hypercholesterolemias, especially FCH and ADH unrelated to LDLR or APOB defects.

• Authors: A L García-Otín, M Cofán, M Junyent, D Recalde, A Cenarro, M Pocoví, E Ros, F Civeira
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 92 Issue 9 Pg. 3667-73 (Sep 2007) ISSN: 0021-972X [Print] United States
• PMID: 17566095 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins B
• Receptors, LDL
• Sterols
• Cholesterol

Topics

• Adult
• Apolipoproteins B (genetics)
• Cholesterol (metabolism)
• Cross-Sectional Studies
• DNA Mutational Analysis
• Female
• Humans
• Hyperlipoproteinemia Type II (genetics, metabolism)
• Intestinal Absorption (genetics)
• Male
• Middle Aged
• Mutation
• Receptors, LDL (genetics)
• Sterols (metabolism)