Validation of GWAS-associated loci for coronary artery disease in the Russian population and pharmacogenetic analysis of their effects during the lipid-lowering therapy with rosuvastatin

Background. Single nucleotide polymorphisms (SNPs) rs9982601 (KCNE2), rs17087335 (NOA1), and rs2048327 (SLC22A3) have been associated with the risk of coronary artery disease (CAD) in genome-wide association studies (GWAS), but have not previously been studied for their impact on the efficacy of rosuvastatin therapy.
Aim: to establish the association of these SNPs with the effectiveness of lipid-lowering rosuvastatin therapy and to validate their association with the risk of CAD in the population of Central Russia.
Methods. 1960 individuals were included in CAD risk study; 116 patients with CAD were included in the pharmacogenetic study. The change in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) was studied during 1, 6, and 12 months of rosuvastatin therapy. SNP genotyping was performed using the MassARRAY 4 genomic mass spectrometer and real-time polymerase chain reaction. The association of SNPs with the risk of CAD and with change in lipid levels was analyzed using logistic and linear regression, respectively, in PLINK v1.9 software.
Results. SNP rs9982601 was associated with the enhanced lipid-lowering effect of rosuvastatin in terms of TC reduction (p = 0,046). The association of above SNP with CAD risk was validated (OR 4,23 95% CI = 1,91-9,40; p<0,001). Rs17087335 and rs2048327 SNPs were associated neither with rosuvastatin efficacy nor CAD risk.
Conclusion. For the first time, the influence of GWAS-associated locus for CAD rs9982601 (KCNE2) on the lipid-lowering effect of rosuvastatin was established, and its association with the risk of CAD in residents of Central Russia was validated.

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