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

The response to therapy with hypolipidemic agents shows considerable indivi dual variation. These differences may be due to the interaction of environm ental and genetic factors that affect drug bioavailability, receptor functi on or ligand structure. Our objective was to assess the effect of apolipopr otein (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-bli nd clinical trial, and received 10 mg/day of atorvastatin. Our data demonst rate no significant gender differences for LDL cholesterol levels at baseli ne. 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 basel ine. However, men carrying the epsilon2 allele had a significantly higher m ean LDL-C response (-44%) than epsilon3 homozygotes (-37%) and epsilon4 car riers (-34%); P = 0.01 for apoE group by treatment interaction. No such gen e/treatment interactions were noted in women, with those carrying the epsil on2 allele showing a similar mean response (-34%) as epsilon3 homozygotes ( -39%) and epsilon4 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 e2 carriers being more responsive (-27%) than epsilon3/3 ( -13%) and epsilon4 (-22%). This interaction was no t 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 ther apy in men, but not in women. (C) 2001 Elsevier Science Ireland Ltd. All ri ghts reserved.