Response to HMG CoA reductase inhibitors in heterozygous familial hypercholesterolemia due to the 10-kb deletion ('French Canadian mutation') of the LDL receptor gene
Autor: | Ghislaine Roederer, Jacques Genest, Shiqiang Qiu, L. Karayan, Robert Dufour, Jean Davignon, C. Betard, Anne Minnich |
---|---|
Rok vydání: | 1994 |
Předmět: |
Adult
Male Heterozygote Familial hypercholesterolemia Reductase medicine.disease_cause Hyperlipoproteinemia Type II chemistry.chemical_compound medicine Humans Enzyme Inhibitors Allele Genetics Mutation biology Cholesterol Cholesterol LDL Middle Aged medicine.disease Null allele Receptors LDL chemistry LDL receptor HMG-CoA reductase biology.protein Female lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors Cardiology and Cardiovascular Medicine Gene Deletion |
Zdroj: | Arteriosclerosis and Thrombosis: A Journal of Vascular Biology. 14:1258-1263 |
ISSN: | 1049-8834 |
Popis: | The 10-kb deletion ("French Canadian mutation") of the low-density lipoprotein (LDL) receptor gene is the most common mutation causing familial hypercholesterolemia among subjects of French Canadian descent. In affected subjects, it results in a null allele of the LDL receptor gene and provides a unique opportunity to examine single-allele regulation of this gene in humans. We sought to ascertain the response of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in subjects with the French Canadian mutation of the LDL receptor gene and to correlate this response with biochemical variables and the haplotype of the nondeletion LDL receptor allele. The prevalence of non-responders to high doses of HMG CoA reductase inhibitors (defined as < 15% decrease in LDL cholesterol [LDL-C] from baseline values after dietary intervention) was ascertained in 105 patients heterozygous for the 10-kb deletion after excluding first-degree relatives and those on combined lipid-lowering therapy or other lipid-lowering agents. Lipoprotein cholesterol levels were examined after a diet period (30% calories as fat) and after receiving HMG CoA reductase inhibitors as mono-therapy for a minimum of 3 months. The mean reduction in total cholesterol was 45 +/- 23%, in LDL-C 33 +/- 15%, and in triglycerides 32 +/- 49% (all P < .005). There was a slight increase in high-density lipoprotein cholesterol of 8.5 +/- 18% (P > .05).(ABSTRACT TRUNCATED AT 250 WORDS) |
Databáze: | OpenAIRE |
Externí odkaz: |