Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Lipid-Associated GWAS Loci Predict Antiatherogenic Effects of Rosuvastatin in Patients with Coronary Artery Disease

Version 1 : Received: 18 May 2023 / Approved: 19 May 2023 / Online: 19 May 2023 (03:26:56 CEST)

A peer-reviewed article of this Preprint also exists.

Kononov, S.; Azarova, I.; Klyosova, E.; Bykanova, M.; Churnosov, M.; Solodilova, M.; Polonikov, A. Lipid-Associated GWAS Loci Predict Antiatherogenic Effects of Rosuvastatin in Patients with Coronary Artery Disease. Genes 2023, 14, 1259. Kononov, S.; Azarova, I.; Klyosova, E.; Bykanova, M.; Churnosov, M.; Solodilova, M.; Polonikov, A. Lipid-Associated GWAS Loci Predict Antiatherogenic Effects of Rosuvastatin in Patients with Coronary Artery Disease. Genes 2023, 14, 1259.

Abstract

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 P-values were calculated through adaptive permutation tests. Over one-year 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, the polymorphisms rs1689800, rs55730499, rs11220463, and rs16942887 were found to be predictive markers for multiple antiatherogenic effects of rosuvastatin in CAD patients.

Keywords

coronary artery disease; plasma lipids; carotid intima-media thickness; pharmacogenetics; personalized medicine; single nucleotide polymorphisms; lipid-lowering therapy; rosuvastatin.

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

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