S19W apolipoprotein A5 gene polymorphism and efficiency of atorvastatin and fenofibrate in type 2 diabetes mellitus

Objective. To compare the efficiency of atorvastatin monotherapy and combined therapy (atorvastatin and fenofibrate) in type 2 diabetes mellitus (T2DM) depending on the genotype of S19W apolipoprotein A5 gene polymorphism (APOA5).

Design and methods. Altogether 135 patients with T2DM were enrolled, 114 women and 21 men (mean age 59,3 ± 0,3 years) taking biguanides, with HbA1c < 8,0 %. None of them received lipid-lowering therapy. Clinical data, serum lipids and genetic variants of АPOА5 were assessed. Atorvastatin monotherapy (20 mg/day/3 months) was initially prescribed with subsequent change to the combination therapy by atorvastatin and fenofibrate (20 mg + 145 mg/day/3 months).

Results. Three-month monotherapy led to a significant reduction in triglycerides (TG) and very low density lipoproteins cholesterol (VLDL-cholesterol) levels in patients with SS genotype compared to carriers of SW genotype (p = 0,015 and p = 0,025, respectively). At the same time, after 3‑month combination therapy no differences were found between АPOА5 variants. There was a trend towards greater reduction in total cholesterol, TG, and VLDL-cholesterol in SW-carriers compared to SS-carriers. There was a paradoxical decrease in high density lipoproteins cholesterol (HDL-cholesterol) in patients with SW genotype, while it remained unchanged in patients with SS genotype.

Conclusions. Our results suggest that polymorphic variants in АPOА5 may affect pharmacogenetics of lipid-lowering therapy in T2DM.

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