Polymorphic rs7412 in APOE gene as a predictor of ischemic heart disease risk and effectiveness of Rosuvastatin therapy

Objective. The aim of the study was to evaluate the effectiveness of the hypolipidemic therapy with Rosuvastatin in patients, suffering from ischemic heart disease (IHD), II-III class stable angina, and to estimate the risk of IHD development among the inhabitants of Central Russia taking into account carriers of APOE rs7412 gene variant. Materials and methods. We participated 144 patients in pharmacogenetic study, aged 40-70 years, who were prescribed Rosuvastatin in initial dose 5 mg daily with gradual increase up to 10-20-40 mg to attain the target lipid levels in accordance with national recommendations. To estimate IHD risk we used 669 DNA samples, taken from IHD patients and relatively healthy individuals. We estimated the association between genotype and hypolipidemic effect of Rosuvastatin in IHD patients using linear regression, corrected by sex, age, body mass index (BMI), and Rosuvastatin dose. The influence of genotype on IHD risk was estimated using logistic regression. Results. The presence of APOE rs7412 C/T and T/T genotypes was associated with decreased IHD risk (OR=0.51 95% CI 0.30-0.87, P =0.013). IHD patients, being homozygotes in rs7412 had higher initial total cholesterol (TC) levels ( P =0.049) in interaction with age and BMI. T/T genotype was associated with increased response to Rosuvastatin in terms of TC in 1 month ( P =0.0022) and 12 months of therapy ( P =0.037), and in terms of low-density lipoprotein cholesterol (LDL-C) in 1 ( P =0.0018) and 6 months ( P =0.043). Conclusion. We have found the association between APOE rs7412 polymorphism and hypolipidemic effect of Rosuvastatin in IHD patients, and IHD risk in inhabitants of Central Russia.

ишемическая болезнь сердца, APOE, розувастатин, фармакогенетика, холестерин, липопротеиды низкой плотности, риск, Rosuvastatin, CAD, APOE, ischemic heart disease, pharmacogenetics, risk, LDL-C, cholesterol