Apolipoprotein E genotype affects plasma lipid response to atorvastatin in a gender specific manner

The response to therapy with hypolipidemic agents shows considerable individual variation. These differences may be due to the interaction of environmental and genetic factors that affect drug bioavailability, receptor function or ligand structure. Our objective was to assess the effect of apolipoprotein (apo) E genotype and gender on lipid-lowering response to the HMG CoA reductase inhibitor, atorvastatin. Genotyping was carried out on DNA from 328 male and female subjects who participated in a multicentric, double-blind clinical trial, and received 10 mg/day of atorvastatin. Our data demonstrate no significant gender differences for LDL cholesterol levels at baseline. Moreover, mean LDL-C lowering was similar in men (−36.2%, range −2.7 to −57.8%) and in women (−38.1%, range −9.5 to −58.5%) as compared to baseline. However, men carrying the 2 allele had a significantly higher mean LDL-C response (−44%) than 3 homozygotes (−37%) and 4 carriers (−34%); P=0.01 for apoE group by treatment interaction. No such gene/treatment interactions were noted in women, with those carrying the 2 allele showing a similar mean response (−34%) as 3 homozygotes (−39%) and 4 carriers (−34%). Mean plasma triglyceride lowering with atorvastatin was 17%. A significant apoE group by treatment interaction (P=0.010) was also observed in men, with 2 carriers being more responsive (−27%) than 3/3 (−13%) and 4 (−22%). This interaction was not observed in women. In summary, atorvastatin treatment had similar effects on plasma lipid levels in both men and women; however, the apoE gene locus was a significant predictor of LDL-C and TG responses to atorvastatin therapy in men, but not in women.