Genetic variants associated with angiotensin-converting enzyme inhibitor-associated angioedema

Guillaume Pare, Michiaki Kubo, James B. Byrd, Catherine A. McCarty, Alencia Woodard-Grice, Koon K. Teo, Sonia S. Anand, Rebecca L. Zuvich, Yuki Bradford, Stephanie Ross, Yusuke Nakamura, Marylyn Ritchie, Nancy J. Brown

研究成果: ジャーナルへの寄稿学術論文査読

65 被引用数 (Scopus)

抄録

Objective: The objective of this study was to identify genetic variants associated with angiotensin-converting enzyme (ACE) inhibitor-associated angioedema. Participants and Methods: We carried out a genome-wide association study in 175 individuals with ACE inhibitor-associated angioedema and 489 ACE inhibitor-exposed controls from Nashville (Tennessee) and Marshfield (Wisconsin). We tested for replication in 19 cases and 57 controls who participated in Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET). Results: There were no genome-wide significant associations of any single-nucleotide polymorphism (SNP) with angioedema. Sixteen SNPs in African Americans and 41 SNPs in European Americans were associated moderately with angioedema (P<10) and evaluated for association in ONTARGET. The T allele of rs500766 in PRKCQ was associated with a reduced risk, whereas the G allele of rs2724635 in ETV6 was associated with an increased risk of ACE inhibitor-associated angioedema in the Nashville/Marshfield sample and ONTARGET. In a candidate gene analysis, rs989692 in the gene encoding neprilysin (MME), an enzyme that degrades bradykinin and substance P, was significantly associated with angioedema in ONTARGET and Nashville/Marshfield African Americans. Conclusion: Unlike other serious adverse drug effects, ACE inhibitor-associated angioedema is not associated with a variant with a large effect size. Variants in MME and genes involved in immune regulation may be associated with ACE inhibitor-associated angioedema.

本文言語英語
ページ(範囲)470-478
ページ数9
ジャーナルPharmacogenetics and genomics
23
9
DOI
出版ステータス出版済み - 09-2013
外部発表はい

All Science Journal Classification (ASJC) codes

  • 遺伝学(臨床)
  • 薬理学、毒性学および薬学一般
  • 遺伝学
  • 分子医療
  • 分子生物学

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