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Genetic Variants Associated with Adverse Events after Angiotensin-Converting Enzyme Inhibitor Use: Replication after GWAS-Based Discovery

Yonsei Medical Journal, 2022, 63(4), , pp.342-348 [Peer Reviewed Journal]

COPYRIGHT(C) KYOBO BOOK CENTRE ALL RIGHTS RESERVED ;Copyright: Yonsei University College of Medicine 2022. ;Copyright: Yonsei University College of Medicine 2022 2022 Yonsei University College of Medicine ;ISSN: 0513-5796 ;EISSN: 1976-2437 ;DOI: 10.3349/ymj.2022.63.4.342 ;PMID: 35352885

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  • Title:
    Genetic Variants Associated with Adverse Events after Angiotensin-Converting Enzyme Inhibitor Use: Replication after GWAS-Based Discovery
  • Author: 이찬주 ; 최보금 ; 박하연 ; 박정미 ; 이지현 ; 이상학
  • Subjects: Angiotensin-Converting Enzyme Inhibitors - adverse effects ; Asians - genetics ; Cough - chemically induced ; Cough - drug therapy ; Cough - genetics ; Genome-Wide Association Study ; Humans ; Original ; Polymorphism, Single Nucleotide - genetics ; Transcription Factors - genetics ; 의학일반
  • Is Part Of: Yonsei Medical Journal, 2022, 63(4), , pp.342-348
  • Description: 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. 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. Five genes, namely , , , , and , were identified near variants associated with ACEI-related 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 , , intron, and , respectively) were significantly associated with both categories of AEs. 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.
  • Publisher: Korea (South): 연세대학교의과대학
  • Language: Korean;English
  • Identifier: ISSN: 0513-5796
    EISSN: 1976-2437
    DOI: 10.3349/ymj.2022.63.4.342
    PMID: 35352885
  • Source: KoreaMed (Open access)
    KoreaMed Synapse(OpenAccess)
    PubMed Central (Open access)
    DOAJ Directory of Open Access Journals
    Geneva Foundation Free Medical Journals at publisher websites
    MEDLINE
    ROAD: Directory of Open Access Scholarly Resources
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