POLYMORPHISMS RS1004467 AND RS11191548 AT CYP17A1 ARE ASSOCIATED WITH EARLY HYPOLIPIDEMIC RESPONSE TO ROSUVASTATIN THERAPY

Background. Polymorphisms of the CYP17A1 gene are known for their association with the risk of coronary artery disease (CAD), and essential hypertension (EH), dyslipidemia, and with the levels of sex hormones. However, pharmacogenetics aspects of these polymorphisms have not so far been investigated. Objective. To study the association of rs1004467 and rs11191548 variants at CYP17A1 with the effectiveness of rosuvastatin therapy in terms of change in plasma lipids and carotid intima-media thickness (CIMT), and the association with the risk of CAD and EH in Russians. Design and methods. The pharmacogenetics study included 116 patients with CAD, stable angina pectoris, observation period was 12 months; genetic association study — 749 patients with CAD, 737 EH patients. Genotyping was performed using the MassARRAY-4 system. Results. Both CYP17A1 polymorphisms were not associated with CAD and EH risk. The most significant associations with the attenuated decrease in LDL-C were observed in 1 month of therapy (in variant homozygotes of both polymorphisms, p = 0,0002), and with triglyceride level change in 6 months (in heterozygotes of rs1004467 and rs11191548, p = 0,0015 и 0,0013, respectively). Attenuated CIMT regression in 6 months was associated with rs11191548 variant (p = 0,034). Conclusion. We have found for the first time the associations of rs1004467 and rs11191548 of CYP17A1 with the effectiveness of rosuvastatin therapy, and the associations were the strongest in the early period of treatment.

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