APOE gene polymorphism is a risk factor for dyslipidemia and potential pharmacogenetic marker of lipid-lowering therapy

Abstract

Aim. APOE genotype is widely discussed as a risk factor for lipid disorders and cardiovascular disease pathogenesis of which is atherosclerosis. Statins are the most widely used group of drugs for the treatment of hyperlipidemia and prevention of the atherothrombotic cardiovascular complications. Our purpose is to investigate the role of polymorphisms ε2/ε3/ε4 APOE gene in the risk of hyperlipidemia and its impact on the effectiveness and safety of statin therapy in Russian.
Materials and methods: Genotype APOE was determined in 152 patients, with hyperlipidemia IIa and IIb the WHO types, with evaluation on a scale SCORE high cardiovascular risk and 268 people of population control. For the 107 patients were identified dynamic indicators of clinical and biochemical parameters after 3 months of statin therapy. Efficacy of therapy based on the genotype APOE was investigated on a group of 59 patients receiving 10mg of rosuvastatin based on the change in total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) after 3 months of treatment.
Results: Revealed a protective effect of APOE genotype ε3/ε3 against hyperlipidemia IIa and IIb risk, the relative risk (RR) was 0.69, (p=0.031). Among patients with disorders of lipid metabolism (hypercholesterolemia and/ or an increase in atherogenic index and some additional hypertriglyceridemia), APOE ε3 genotype is associated with better lipid profile: lower level of LDL and TG, (p=0,002 p=0,04 respectively). APOE allele ε2 was a risk factor for type IIb hyperlipidemia (RR=4.15, p=0.00044) compared with carriers of genotype ε3/ε3. APOE genotype had no effect on the change in cholesterol levels after 3 months use of rosuvastatin 10 mg (p=0,46). It was identified, APOE ε4 allele carriers, association with idiopathic muscle pain in patients who received statin therapy (OR=3.40, p=0.028).
Conclusions: APOE ε3/ε3 genotype ε3 is a protective factor for the hyperlipidemia IIa and IIb. APOE ε2 allele is a risk factor not only for the type III, but also for the type IIb hyperlipidemia. Research APOE genotype may be useful to assess the risk of cardiovascular disease, and to identify patients with additional risk factor statin-induced myopathy.