Purpose: Angiotensin-converting enzyme inhibitors (ACEIs) are medications generally prescribed for patients with high cardiovascular risk; however, they are suboptimally used due to frequent adverse events (AEs). The present study aimed to identify and replicate 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 replication through target sequencing was used. In total, 1300 individuals received ACEIs from 2001 to 2007; among these, 228 were selected for 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 PharmGKB database. 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 ACEIrelated AEs. 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 SNPs and rs147912715 exhibited associations with ACEI-related cough, whereas four SNPs (rs5224, rs81767786, rs10766756, and rs4974539 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 associations with ACEI-related AEs. These results provide rare and clinically relevant information for safer use of ACEIs.

Purpose: Advanced pediatric emergency centers play an important role in professional treatment of children. We analyzed the characteristics of children who visited an advanced pediatric emergency center. Methods: The study enrolled children younger than 15 years who had visited Keimyung University Dongsan Medical advanced pediatric emergency center between April 2016 and March 2018. We reviewed the children’s age group characteristics, time of visit, triage results by the Korean Triage and Acuity Scale (KTAS), use of the emergency medical service ambulances, emergency department length of stay, final diagnosis, and final disposition. Results: A total 41,355 children (mean age of 3.1 ± 3.0 years) were enrolled, and those aged 1-4 years accounted for 65.7%. The visit was most frequent in December, at night (40.2%), and at holiday hours (30.2%) (c.f., business hours, 11.5%). Fever (33.2%) and eyelid laceration (11.5%) were the most common final diagnoses of diseases and injuries, respectively. The children triaged as the KTAS 1-2 accounted for 5.9% of the study children (c.f., KTAS 3-4, 91.5%). According to time of visit, the proportion of hospitalization (31.4%) and transfer from other hospitals (34.7%) were most frequent at business hours than other times of visit (P < 0.001). Conclusion The children tended to visit the center with minor diseases or injuries, especially during holidays and at night. Further research is needed for optimizing the roles of advanced pediatric emergency centers, taking into account the characteristics of patients and demand for the centers.