Pharmacogenetics of statin therapy and the endothelial function parameters in patients with type 2 diabetes mellitus

Abstract

Aim. To investigate the association of variation in lipid-lowering response and endothelial function (EF) parameters after atorvastatin therapy in patients with type 2 diabetes mellitus (T2DM) with genetic markers of atherosclerosis. Methods. We included 97 patients with T2DM who were prescribed atorvastatin. Fasting lipid profiles and EF parameters were assessed before and after 12 months of statin therapy. For EF evaluation, we performed pulse-wave analysis during reactive hyperaemia. The genotypes for polymorphic markers were identified by real-time polymerase chain reaction with TaqMan probes. The statistical analysis included Wilcoxon, Mann-Whitney and Kruskal-Wallis tests. P-values < 0.05 were considered statistically significant. Results. With statin therapy, PPARG2Pro/Pro patients had significantly lower TC and LDL-C levels than PPARG2 Pro/Ala and PPARG2 Ala/Ala patients (TC: 20.74% vs. 4.6% and 5.61%; p = 0.04 and LDL-C: 26.00% vs. 6.11% and 7.32%; p = 0.029). Patients with APOEE4/E4 had significantly lower TC and TG levels than other APOE patients (TC: -46.25% for E4/ E4 vs. +33.33% for E4/E2, +5.73% for E3/E2, +11.80% for E3/E4, -10.92% for E3/E3, p = 0,01; TG: -56.52% for E4/ E4 vs. +24.43% for E4/E2, +19.63% for E3/E2, +8.05% for E3/E4, -20.00% for E3/E3, p = 0.04). The patients with GG for TNFα G(238)A and GA for TNFα G(308)A had significantly greater amplitude of post-occlusive wave increase (Apw) than patients with GA for TNFα G(238)A and GG for TNF G(308)A (+8.16 % vs. -0.93%, E = 0,04; +44% vs. -4.4%, p = 0.004, respectively). Conclusion. PPARG2Pro12Ala and APOEE E2/E3/E4 polymorphism contributed to the between-patient variability in the response to statin therapy in patients with T2DM. Significant associations of the TNFα gene polymorphism with EF in patients with T2DM suggest an important role of inflammation in the pathogenesis of MVD.