Genetics
CETP haplotype independently predicts triglyceride response to fluvastatin in familial hypercholesterolemia (Atherosclerosis 2005)
Original title: The association of common SNPs and haplotypes in the CETP and MDR1 genes with lipids response to fluvastatin in familial hypercholesterolemia
In 76 patients with familial hypercholesterolemia treated with fluvastatin 40 mg for 20 weeks, mean LDL-cholesterol fell 21.5%, triglyceride fell 8.3%, and HDL-cholesterol rose 13.4%. Five tagging SNPs each in CETP and the drug transporter MDR1 reconstructed haplotypes covering 71.4% and 90.2% of observed variation respectively. CETP-H13 and MDR1-h4 were associated with a greater LDL-C response, while CETP-H5 was significantly associated with a smaller decrease in triglyceride and HDL-C response, and MDR1-h10 with a smaller triglyceride decrease; multivariate regression showed CETP-H5 and MDR1-h10 had independent, additive effects on triglyceride response. CETP and MDR1 genotype thus independently shape the lipid response to fluvastatin.
Original abstract
Objective: To examine whether genetic polymorphisms in the cholesteryl-ester transfer protein (CETP) and the P-glycoprotein drug transporter (MDR1), are associated with variable lipid response to fluvastatin.
Methods: Lipid levels were determined in a compliance-monitored clinical study at baseline and following 20 weeks of treatment with 40 mg dose of fluvastatin in 76 FH patients. CETP and MDR1 SNP genotyping was performed and linear regression was used to examine the associations between common SNPs and haplotypes and lipid response.
Results: Treatment with 40 mg of fluvastatin resulted in mean low density lipoprotein cholesterol (LDL-C) reduction of 21.5%; mean triglyceride (TG) reduction of 8.3%; and a mean high-density lipoprotein cholesterol (HDL-C) increase of 13.4%. Five tagging SNPs in both genes were used to reconstruct five and six haplotypes accounting for 71.4% and 90.2% of the observed haplotypes in the CETP and MDR1 genes, respectively. CETP-H13 and MDR1-h4 were associated with an increase in LDL-C response. CETP-H5 was significantly associated with decreased TG and HDL-C response, whereas MDR1-h10 was associated with decreased TG response. A multivariate regression model indicated an independent additive effect of CETP-H5 and MDR1-h10 on the level of TG response.
Conclusions: CETP and MDR1 have independent effects on lipid changes following fluvastatin treatment. The results of this study may lead to an improved understanding of the genetic determinants of lipids response to treatment.
familial hypercholesterolaemiageneticsstatins
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.