Pharmacogenetics of statin therapy and the endothelial function parameters in patients with type 2 diabetes mellitus
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 ator...
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Endocrinology Research Centre
2016-07-01
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| Series: | Сахарный диабет |
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| Online Access: | https://www.dia-endojournals.ru/jour/article/view/7851 |
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| author | Nadezhda O. Lebedeva Olga K. Vikulova Alexei G. Nikitin Minara Sh. Shamkhalova Marina V. Shestakova Ivan I. Dedov |
| author_facet | Nadezhda O. Lebedeva Olga K. Vikulova Alexei G. Nikitin Minara Sh. Shamkhalova Marina V. Shestakova Ivan I. Dedov |
| author_sort | Nadezhda O. Lebedeva |
| collection | DOAJ |
| description | 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 АРОЕЕ4/Е4 had significantly lower TC and TG levels than other АРОЕ patients (TC: -46.25% for Е4/Е4 vs. +33.33% for Е4/Е2, +5.73% for Е3/Е2, +11.80% for Е3/Е4, -10.92% for Е3/Е3, р = 0,01; TG: -56.52% for Е4/Е4 vs. +24.43% for Е4/Е2, +19.63% for Е3/Е2, +8.05% for Е3/Е4, -20.00% for Е3/Е3, р = 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 TNFα G(308)A (+8.16 % vs. -0.93%, р = 0,04; +44% vs. -4.4%, p = 0.004, respectively).Conclusion. PPARG2Pro12Ala and АРОЕE2/Е3/Е4 polymorphism contributed to the between-patient variability in the response to statin therapy in patients with T2DM. Significant associations of the TNFαgene polymorphism with EF in patients with T2DM suggest an important role of inflammation in the pathogenesis of MVD. |
| first_indexed | 2024-03-08T15:19:50Z |
| format | Article |
| id | doaj.art-036503a760eb48cb90d3b24cb9ff6ded |
| institution | Directory Open Access Journal |
| issn | 2072-0351 2072-0378 |
| language | English |
| last_indexed | 2024-04-24T22:01:50Z |
| publishDate | 2016-07-01 |
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| series | Сахарный диабет |
| spelling | doaj.art-036503a760eb48cb90d3b24cb9ff6ded2024-03-20T11:48:00ZengEndocrinology Research CentreСахарный диабет2072-03512072-03782016-07-0119320421110.14341/DM200342-77367Pharmacogenetics of statin therapy and the endothelial function parameters in patients with type 2 diabetes mellitusNadezhda O. Lebedeva0Olga K. Vikulova1Alexei G. Nikitin2Minara Sh. Shamkhalova3Marina V. Shestakova4Ivan I. Dedov5I.M. Sechenov First Moscow State Medical UniversityEndocrinology Research Centre; I.M. Sechenov First Moscow State Medical UniversityFederal Research Clinical Center of Federal Medical and Biological Agency of RussiaEndocrinology Research CentreEndocrinology Research Centre; I.M. Sechenov First Moscow State Medical UniversityEndocrinology Research CentreAim. 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 АРОЕЕ4/Е4 had significantly lower TC and TG levels than other АРОЕ patients (TC: -46.25% for Е4/Е4 vs. +33.33% for Е4/Е2, +5.73% for Е3/Е2, +11.80% for Е3/Е4, -10.92% for Е3/Е3, р = 0,01; TG: -56.52% for Е4/Е4 vs. +24.43% for Е4/Е2, +19.63% for Е3/Е2, +8.05% for Е3/Е4, -20.00% for Е3/Е3, р = 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 TNFα G(308)A (+8.16 % vs. -0.93%, р = 0,04; +44% vs. -4.4%, p = 0.004, respectively).Conclusion. PPARG2Pro12Ala and АРОЕE2/Е3/Е4 polymorphism contributed to the between-patient variability in the response to statin therapy in patients with T2DM. Significant associations of the TNFαgene polymorphism with EF in patients with T2DM suggest an important role of inflammation in the pathogenesis of MVD.https://www.dia-endojournals.ru/jour/article/view/7851statinsendothelial functiont2dpolymorphic markersgenes pparg2apoetnf-α |
| spellingShingle | Nadezhda O. Lebedeva Olga K. Vikulova Alexei G. Nikitin Minara Sh. Shamkhalova Marina V. Shestakova Ivan I. Dedov Pharmacogenetics of statin therapy and the endothelial function parameters in patients with type 2 diabetes mellitus Сахарный диабет statins endothelial function t2d polymorphic markers genes pparg2 apoe tnf-α |
| title | Pharmacogenetics of statin therapy and the endothelial function parameters in patients with type 2 diabetes mellitus |
| title_full | Pharmacogenetics of statin therapy and the endothelial function parameters in patients with type 2 diabetes mellitus |
| title_fullStr | Pharmacogenetics of statin therapy and the endothelial function parameters in patients with type 2 diabetes mellitus |
| title_full_unstemmed | Pharmacogenetics of statin therapy and the endothelial function parameters in patients with type 2 diabetes mellitus |
| title_short | Pharmacogenetics of statin therapy and the endothelial function parameters in patients with type 2 diabetes mellitus |
| title_sort | pharmacogenetics of statin therapy and the endothelial function parameters in patients with type 2 diabetes mellitus |
| topic | statins endothelial function t2d polymorphic markers genes pparg2 apoe tnf-α |
| url | https://www.dia-endojournals.ru/jour/article/view/7851 |
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