GWAS of Statin response
Cardiovascular disease (CVD) is one of the main causes of death in the world. The increased level of blood cholesterol is significantly correlated to CVD occurrence. Statins are a group of drugs that decrease the synthesis of cholesterol in the liver by inhibiting the final enzyme of the pathway named HMG-CoA reductase. Several investigations showed that different patients give different responses to the administration of these drugs according to their genetic background. In this research study, using Genome-Wide Association Studies (GWAS) data analysis methods, such as the SimpleM statistical approach and genomic connection matrix, we tried to discover the novel candidate SNPs that were involed in response to statin drugs. This investigation was carried out using 3,221 cardiovascular diseses patients data about genotypes and phenotypes of two important parameters, total cholesterol and LDL level, in response to statin administration. Functional annotation of nearest genes to candidate SNPs also was carried out by using comprehensive databases and tools such as BioMart-Ensembl, UCSC, NCBI, and WebGestalt software. Our results represented eight novel SNPs (rs10820084, rs4803750, rs10989887, rs1966503, rs17502794, rs10785232, rs484071, rs4785621) significantly associated with statin response in different individuals with cardiovascular disease for the first time. In addition, some groups of genes that are close to the SNPs were also represented and evaluated. Based on our results, some of these genes such as BAAT, BCL3, and CMTM6 have a direct functional impact on cholesterol level or LDL biosynthesis that confirmed the effects of nighbor SNPs on the response to statin drugs. Today, finding the genes and molecular mechanisms involved in the response to drugs is of great importance in personalized medicine.