薬理ゲノミクスと薬理プロテオミクスのジャーナル

概要

The Cholesteryl Ester Transfer Protein (CETP) Taqib and I405V Gene Polymorphisms and Statin Treatment

Bousoula Eleni, Kolovou Vana, Boutsikou Maria,Tapola Anastasia, Perrea Despoina and Kolovou Genovefa

Background: CETP (cholesterol ester transfer protein) is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. It is composed mainly at the liver and it collects triglycerides from chylomicrons and VLDL and exchanges them for cholesteryl esters from HDL. By this mean, very dense LDL molecules are being formed. The latter are very atherogenetic factors. The gene encoding CETP is located on the long (q) arm of chromosome 16 at position 21. It has been found that at least two polymorphisms in this gene, TaqIB (with B1B1, B1B2 and B2B2 genotypes) and I405V (with II, IV and VV genotypes), have been associated with different response to statin treatment. Aim: The aim of this study was to investigate a probable correlation of the aforementioned CETP gene polymorphisms with better or worse response to two specific statins: simvastatin and atorvastatin. Methods: The DNA of 78 subjects, 53 men (67.9%) and 25 women (32.1%) of mean age 57±20 years with dyslipidemia, was analyzed for the different genotypes of the CETP gene polymorphisms TaqIB and I405V. To all these patients simvastatin and atorvastatin were administered as lipid lower agents and they had a lipid profil test four times during the study period. Namely, before the beginning of the therapy, two months after taking the first statin (either simvastatin or atorvastatin), two months after they quitted therapy and last time two months after restarting the lipid lower therapy with the other statin. Results: Both statins administered to patients succeeded to reduce significantly total cholesterol, triglycerides and LDL-C levels and simultaneously to augment significantly HDL-C levels. These changes have been observed in all patients independently of their genotype of the two studied CETP gene polymorphisms. No significant differences were demonstrated in total cholesterol, triglycerides, HDL-C and LDL-C levels before and after simvastatin and atorvastatin therapy across Taq1B and I405V genotypes. Moreover, the effect of age and gender on lipid levels, independently of which statin was used or the genotype, was not significant. Conclusion: The initial hypothesis of our study, that there is a probable correlation between different genotypes of TaqIB and I405V CETP gene polymorphisms and response to treatment with simvastatin and atorvastatin was not confirmed.