Cardiovascular disease-associated loci as pharmacogenetic markers for the efficacy of hypolipidemic therapy with Rosuvastatin

Introduction. Single nucleotide polymorphisms (SNPs) rs4373814 (CACNB2), rs12940887 (ZNF652), rs10850411 (TBX3) are associated with hypertension (HTN) risk, and as part of genetic risk score (GRS) with predisposition to coronary artery disease (CAD).
Aim: to establish the role of these SNPs in the efficacy of rosuvastatin and studying their individual association with CAD and HTN risk.
Methods. 1960 residents of Central Russia were enrolled in CAD and HTN risk study (91% of CAD patients had HTN), 116 CAD patients – in pharmacogenetic study. We assessed total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) change after 1, 6, and 12 months of rosuvastatin therapy. Genotyping was performed on the MassArray-4 System. SNPs association with CAD and HTN risk, and with lipid levels change was estimated by logistic and linear regression, respectively using PLINK v1.90.
Results. Reduced TC-lowering effect of rosuvastatin was associated with rs4373814, rs12940887 (p = 0.019 and 0.014, respectively), and reduced LDL-C-lowering effect – with rs12940887, rs10850411 (p = 0.049 и 0.023, respectively). All SNPs were not associated with CAD risk (p>0.05). The risk of HTN was linked to rs4373814 (p = 0.038).
Conclusions. The association of HTN and CAD (as part of GRS)-associated loci with rosuvastatin pharmacogenetics was established for the first time.

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