Lipid-Associated GWAS Loci Predict Antiatherogenic Effects of Rosuvastatin in Patients with Coronary Artery Disease
We have shown that lipid-associated loci discovered by genome-wide association studies (GWAS) have pleiotropic effects on lipid metabolism, carotid intima-media thickness (CIMT), and CAD risk. Here, we investigated the impact of lipid-associated GWAS loci on the efficacy of rosuvastatin therapy in t...
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MDPI AG
2023-06-01
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| Online Access: | https://www.mdpi.com/2073-4425/14/6/1259 |
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| author | Stanislav Kononov Iuliia Azarova Elena Klyosova Marina Bykanova Mikhail Churnosov Maria Solodilova Alexey Polonikov |
| author_facet | Stanislav Kononov Iuliia Azarova Elena Klyosova Marina Bykanova Mikhail Churnosov Maria Solodilova Alexey Polonikov |
| author_sort | Stanislav Kononov |
| collection | DOAJ |
| description | We have shown that lipid-associated loci discovered by genome-wide association studies (GWAS) have pleiotropic effects on lipid metabolism, carotid intima-media thickness (CIMT), and CAD risk. Here, we investigated the impact of lipid-associated GWAS loci on the efficacy of rosuvastatin therapy in terms of changes in plasma lipid levels and CIMT. The study comprised 116 CAD patients with hypercholesterolemia. CIMT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were measured at baseline and after 6 and 12 months of follow-up, respectively. Genotyping of fifteen lipid-associated GWAS loci was performed by the MassArray-4 System. Linear regression analysis adjusted for sex, age, body mass index, and rosuvastatin dose was used to estimate the phenotypic effects of polymorphisms, and <i>p</i>-values were calculated through adaptive permutation tests by the PLINK software, v1.9. Over one-year rosuvastatin therapy, a decrease in CIMT was linked to rs1689800, rs4846914, rs12328675, rs55730499, rs9987289, rs11220463, rs16942887, and rs881844 polymorphisms (Pperm < 0.05). TC change was associated with rs55730499, rs11220463, and rs6065906; LDL-C change was linked to the rs55730499, rs1689800, and rs16942887 polymorphisms; and TG change was linked to polymorphisms rs838880 and rs1883025 (Pperm < 0.05). In conclusion, polymorphisms rs1689800, rs55730499, rs11220463, and rs16942887 were found to be predictive markers for multiple antiatherogenic effects of rosuvastatin in CAD patients. |
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| spelling | doaj.art-c4188dc6324643f38050d3f15174a2a02023-11-18T10:35:00ZengMDPI AGGenes2073-44252023-06-01146125910.3390/genes14061259Lipid-Associated GWAS Loci Predict Antiatherogenic Effects of Rosuvastatin in Patients with Coronary Artery DiseaseStanislav Kononov0Iuliia Azarova1Elena Klyosova2Marina Bykanova3Mikhail Churnosov4Maria Solodilova5Alexey Polonikov6Department of Internal Medicine No. 2, Kursk State Medical University, 3 Karl Marx Street, 305041 Kursk, RussiaDepartment of Biological Chemistry, Kursk State Medical University, 3 Karl Marx Street, 305041 Kursk, RussiaLaboratory of Biochemical Genetics and Metabolomics, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 18 Yamskaya Street, 305041 Kursk, RussiaDepartment of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, 305041 Kursk, RussiaDepartment of Medical Biological Disciplines, Belgorod State University, 85 Pobedy Street, 308015 Belgorod, RussiaDepartment of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, 305041 Kursk, RussiaDepartment of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, 305041 Kursk, RussiaWe have shown that lipid-associated loci discovered by genome-wide association studies (GWAS) have pleiotropic effects on lipid metabolism, carotid intima-media thickness (CIMT), and CAD risk. Here, we investigated the impact of lipid-associated GWAS loci on the efficacy of rosuvastatin therapy in terms of changes in plasma lipid levels and CIMT. The study comprised 116 CAD patients with hypercholesterolemia. CIMT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were measured at baseline and after 6 and 12 months of follow-up, respectively. Genotyping of fifteen lipid-associated GWAS loci was performed by the MassArray-4 System. Linear regression analysis adjusted for sex, age, body mass index, and rosuvastatin dose was used to estimate the phenotypic effects of polymorphisms, and <i>p</i>-values were calculated through adaptive permutation tests by the PLINK software, v1.9. Over one-year rosuvastatin therapy, a decrease in CIMT was linked to rs1689800, rs4846914, rs12328675, rs55730499, rs9987289, rs11220463, rs16942887, and rs881844 polymorphisms (Pperm < 0.05). TC change was associated with rs55730499, rs11220463, and rs6065906; LDL-C change was linked to the rs55730499, rs1689800, and rs16942887 polymorphisms; and TG change was linked to polymorphisms rs838880 and rs1883025 (Pperm < 0.05). In conclusion, polymorphisms rs1689800, rs55730499, rs11220463, and rs16942887 were found to be predictive markers for multiple antiatherogenic effects of rosuvastatin in CAD patients.https://www.mdpi.com/2073-4425/14/6/1259coronary artery diseaseplasma lipidscarotid intima-media thicknesspharmacogeneticspersonalized medicinesingle nucleotide polymorphisms |
| spellingShingle | Stanislav Kononov Iuliia Azarova Elena Klyosova Marina Bykanova Mikhail Churnosov Maria Solodilova Alexey Polonikov Lipid-Associated GWAS Loci Predict Antiatherogenic Effects of Rosuvastatin in Patients with Coronary Artery Disease Genes coronary artery disease plasma lipids carotid intima-media thickness pharmacogenetics personalized medicine single nucleotide polymorphisms |
| title | Lipid-Associated GWAS Loci Predict Antiatherogenic Effects of Rosuvastatin in Patients with Coronary Artery Disease |
| title_full | Lipid-Associated GWAS Loci Predict Antiatherogenic Effects of Rosuvastatin in Patients with Coronary Artery Disease |
| title_fullStr | Lipid-Associated GWAS Loci Predict Antiatherogenic Effects of Rosuvastatin in Patients with Coronary Artery Disease |
| title_full_unstemmed | Lipid-Associated GWAS Loci Predict Antiatherogenic Effects of Rosuvastatin in Patients with Coronary Artery Disease |
| title_short | Lipid-Associated GWAS Loci Predict Antiatherogenic Effects of Rosuvastatin in Patients with Coronary Artery Disease |
| title_sort | lipid associated gwas loci predict antiatherogenic effects of rosuvastatin in patients with coronary artery disease |
| topic | coronary artery disease plasma lipids carotid intima-media thickness pharmacogenetics personalized medicine single nucleotide polymorphisms |
| url | https://www.mdpi.com/2073-4425/14/6/1259 |
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