초록 열기/닫기 버튼
Purpose: Angiotensin-converting enzyme inhibitors (ACEIs) are medications generally prescribed for patients with high cardiovascularrisk; however, they are suboptimally used due to frequent adverse events (AEs). The present study aimed to identify andreplicate the genetic variants associated with ACEI-related AEs in the Korean population. Materials and Methods: A two-stage approach employing genome-wide association study (GWAS)-based discovery and replicationthrough target sequencing was used. In total, 1300 individuals received ACEIs from 2001 to 2007; among these, 228 were selectedfor GWAS. An additional 336 patients were selected for replication after screening 1186 subjects treated from 2008 to 2018. Candidate genes for target sequencing were selected based on the present GWAS, previous GWASs, and data from the PharmGKBdatabase. Furthermore, association analyses were performed between no AE and AE or cough groups after target sequencing. Results: Five genes, namely CRIM1, NELL1, CACNA1D, VOPP1, and MYBPC1, were identified near variants associated with ACEIrelatedAEs. During target sequencing of 34 candidate genes, six single-nucleotide polymorphisms (SNPs; rs5224, rs8176786,rs10766756, rs561868018, rs4974539, and rs10946364) were replicated for association with all ACEI-related AEs. Four of these SNPsand rs147912715 exhibited associations with ACEI-related cough, whereas four SNPs (rs5224, rs81767786, rs10766756, andrs4974539 near BDKRB2, NELL1, NELL1 intron, and CPN2, respectively) were significantly associated with both categories of AEs. Conclusion: Several variants, including novel and known variants, were successfully replicated and found to have associationswith ACEI-related AEs. These results provide rare and clinically relevant information for safer use of ACEIs.
