Molecular Genetic Screening in Patients With ACE Inhibitor/Angiotensin Receptor Blocker-Induced Angioedema to Explore the Role of Hereditary Angioedema Genes

  1. Mathey, Carina M.
  2. Maj, Carlo
  3. Scheer, Annika B.
  4. Fazaal, Julia
  5. Wedi, Bettina
  6. Wieczorek, Dorothea
  7. Amann, Philipp M.
  8. Löffler, Harald
  9. Koch, Lukas
  10. Schöffl, Clemens
  11. Dickel, Heinrich
  12. Ganjuur, Nomun
  13. Hornung, Thorsten
  14. Forkel, Susann
  15. Greve, Jens
  16. Wurpts, Gerda
  17. Hallberg, Pär
  18. Bygum, Anette
  19. Von Buchwald, Christian
  20. Karawajczyk, Malgorzata
  21. Steffens, Michael
  22. Stingl, Julia
  23. Hoffmann, Per
  24. Heilmann-Heimbach, Stefanie
  25. Mangold, Elisabeth
  26. Ludwig, Kerstin U.
  27. Rasmussen, Eva R.
  28. Wadelius, Mia
  29. Sachs, Bernhardt
  30. Noethen, Markus M.
  31. Forstner, Andreas J.

Download
34_fgene-13-914376.pdf 687,85KB
WeightNameValue
1000 Titel
  • Molecular Genetic Screening in Patients With ACE Inhibitor/Angiotensin Receptor Blocker-Induced Angioedema to Explore the Role of Hereditary Angioedema Genes
1000 Autor/in
  1. Mathey, Carina M. |
  2. Maj, Carlo |
  3. Scheer, Annika B. |
  4. Fazaal, Julia |
  5. Wedi, Bettina |
  6. Wieczorek, Dorothea |
  7. Amann, Philipp M. |
  8. Löffler, Harald |
  9. Koch, Lukas |
  10. Schöffl, Clemens |
  11. Dickel, Heinrich |
  12. Ganjuur, Nomun |
  13. Hornung, Thorsten |
  14. Forkel, Susann |
  15. Greve, Jens |
  16. Wurpts, Gerda |
  17. Hallberg, Pär |
  18. Bygum, Anette |
  19. Von Buchwald, Christian |
  20. Karawajczyk, Malgorzata |
  21. Steffens, Michael |
  22. Stingl, Julia |
  23. Hoffmann, Per |
  24. Heilmann-Heimbach, Stefanie |
  25. Mangold, Elisabeth |
  26. Ludwig, Kerstin U. |
  27. Rasmussen, Eva R. |
  28. Wadelius, Mia |
  29. Sachs, Bernhardt |
  30. Noethen, Markus M. |
  31. Forstner, Andreas J. |
1000 Erscheinungsjahr 2022
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2022-07-18
1000 Erschienen in
1000 Quellenangabe
  • 13:914376
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2022
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.3389/fgene.2022.914376 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339951/ |
1000 Ergänzendes Material
  • https://www.frontiersin.org/articles/10.3389/fgene.2022.914376/full#h13 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Angioedema is a relatively rare but potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As with hereditary forms of angioedema (HAE), this adverse reaction is mediated by bradykinin. Research suggests that ACEi/ARB-induced angioedema has a multifactorial etiology. In addition, recent case reports suggest that some ACEi/ARB-induced angioedema patients may carry pathogenic HAE variants. The aim of the present study was to investigate the possible association between ACEi/ARB-induced angioedema and HAE genes via systematic molecular genetic screening in a large cohort of ACEi/ARB-induced angioedema cases. Targeted re-sequencing of five HAE-associated genes (SERPING1, F12, PLG, ANGPT1, and KNG1) was performed in 212 ACEi/ARB-induced angioedema patients recruited in Germany/Austria, Sweden, and Denmark, and in 352 controls from a German cohort. Among patients, none of the identified variants represented a known pathogenic variant for HAE. Moreover, no significant association with ACEi/ARB-induced angioedema was found for any of the identified common [minor allele frequency (MAF) >5%] or rare (MAF < 5%) variants. However, several non-significant trends suggestive of possible protective effects were observed. The lowest p-value for an individual variant was found in PLG (rs4252129, p.R523W, p = 0.057, p.adjust > 0.999, Fisher’s exact test). Variant p.R523W was found exclusively in controls and has previously been associated with decreased levels of plasminogen, a precursor of plasmin which is part of a pathway directly involved in bradykinin production. In addition, rare, potentially functional variants (MAF < 5%, Phred-scaled combined annotation dependent depletion score >10) showed a nominally significant enrichment in controls both: 1) across all five genes; and 2) in the F12 gene alone. However, these results did not withstand correction for multiple testing. In conclusion, our results suggest that HAE-associated mutations are, at best, a rare cause of ACEi/ARB-induced angioedema. Furthermore, we were unable to identify a significant association between ACEi/ARB-induced angioedema and other variants in the investigated genes. Further studies with larger sample sizes are warranted to draw more definite conclusions concerning variants with limited effect sizes, including protective variants.
1000 Sacherschließung
lokal sequencing
lokal angiotensin-converting enzyme inhibitor
lokal genetics
lokal angiotensin receptor blocker
lokal angioedema
lokal hereditary angioedema
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/TWF0aGV5LCBDYXJpbmEgTS4=|https://frl.publisso.de/adhoc/uri/TWFqLCBDYXJsbw==|https://frl.publisso.de/adhoc/uri/U2NoZWVyLCBBbm5pa2EgQi4=|https://frl.publisso.de/adhoc/uri/RmF6YWFsLCBKdWxpYQ==|https://frl.publisso.de/adhoc/uri/V2VkaSwgQmV0dGluYQ==|https://frl.publisso.de/adhoc/uri/V2llY3pvcmVrLCBEb3JvdGhlYQ==|https://frl.publisso.de/adhoc/uri/QW1hbm4sIFBoaWxpcHAgTS4=|https://frl.publisso.de/adhoc/uri/TMO2ZmZsZXIsIEhhcmFsZA==|https://frl.publisso.de/adhoc/uri/S29jaCwgTHVrYXM=|https://frl.publisso.de/adhoc/uri/U2Now7ZmZmwsIENsZW1lbnM=|https://frl.publisso.de/adhoc/uri/RGlja2VsLCBIZWlucmljaA==|https://frl.publisso.de/adhoc/uri/R2FuanV1ciwgTm9tdW4=|https://frl.publisso.de/adhoc/uri/SG9ybnVuZywgVGhvcnN0ZW4=|https://frl.publisso.de/adhoc/uri/Rm9ya2VsLCBTdXNhbm4=|https://frl.publisso.de/adhoc/uri/R3JldmUsIEplbnM=|https://frl.publisso.de/adhoc/uri/V3VycHRzLCBHZXJkYQ==|https://frl.publisso.de/adhoc/uri/SGFsbGJlcmcsIFDDpHI=|https://frl.publisso.de/adhoc/uri/QnlndW0sIEFuZXR0ZQ==|https://frl.publisso.de/adhoc/uri/Vm9uIEJ1Y2h3YWxkLCBDaHJpc3RpYW4=|https://frl.publisso.de/adhoc/uri/S2FyYXdhamN6eWssIE1hbGdvcnphdGE=|https://frl.publisso.de/adhoc/uri/U3RlZmZlbnMsIE1pY2hhZWw=|https://frl.publisso.de/adhoc/uri/U3RpbmdsLCBKdWxpYQ==|https://frl.publisso.de/adhoc/uri/SG9mZm1hbm4sIFBlcg==|https://frl.publisso.de/adhoc/uri/SGVpbG1hbm4tSGVpbWJhY2gsIFN0ZWZhbmll|https://frl.publisso.de/adhoc/uri/TWFuZ29sZCwgRWxpc2FiZXRo|https://frl.publisso.de/adhoc/uri/THVkd2lnLCBLZXJzdGluIFUu|https://frl.publisso.de/adhoc/uri/UmFzbXVzc2VuLCBFdmEgUi4=|https://frl.publisso.de/adhoc/uri/V2FkZWxpdXMsIE1pYQ==|https://frl.publisso.de/adhoc/uri/U2FjaHMsIEJlcm5oYXJkdA==|https://frl.publisso.de/adhoc/uri/Tm9ldGhlbiwgTWFya3VzIE0u|https://frl.publisso.de/adhoc/uri/Rm9yc3RuZXIsIEFuZHJlYXMgSi4=
1000 Label
1000 Förderer
  1. Bundesinstitut für Arzneimittel und Medizinprodukte |
  2. Medizinische Fakultät, Rheinische Friedrich-Wilhelms-Universität Bonn |
  3. Vetenskapsrådet |
  4. Hjärt-Lungfonden |
  5. The Selander Foundation |
  6. Thuréus stiftelse |
  7. Uppsala Universitet |
  8. Deutsche Forschungsgemeinschaft |
1000 Fördernummer
  1. V-17454/68502/2017-2020 ; V2021.5/68502/2022-2024
  2. V-17454/68502/2017-2020 ; V2021.5/68502/2022-2024
  3. 521-2011-2440 ; 521-2014-3370 ; 2018-03307
  4. 20120557 ; 20140291 ; 20170711
  5. -
  6. -
  7. -
  8. LU 1944/3-1
1000 Förderprogramm
  1. -
  2. -
  3. Medicine
  4. -
  5. -
  6. -
  7. Avtal om Läkarutbildning och Forskning
  8. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Bundesinstitut für Arzneimittel und Medizinprodukte |
    1000 Förderprogramm -
    1000 Fördernummer V-17454/68502/2017-2020 ; V2021.5/68502/2022-2024
  2. 1000 joinedFunding-child
    1000 Förderer Medizinische Fakultät, Rheinische Friedrich-Wilhelms-Universität Bonn |
    1000 Förderprogramm -
    1000 Fördernummer V-17454/68502/2017-2020 ; V2021.5/68502/2022-2024
  3. 1000 joinedFunding-child
    1000 Förderer Vetenskapsrådet |
    1000 Förderprogramm Medicine
    1000 Fördernummer 521-2011-2440 ; 521-2014-3370 ; 2018-03307
  4. 1000 joinedFunding-child
    1000 Förderer Hjärt-Lungfonden |
    1000 Förderprogramm -
    1000 Fördernummer 20120557 ; 20140291 ; 20170711
  5. 1000 joinedFunding-child
    1000 Förderer The Selander Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  6. 1000 joinedFunding-child
    1000 Förderer Thuréus stiftelse |
    1000 Förderprogramm -
    1000 Fördernummer -
  7. 1000 joinedFunding-child
    1000 Förderer Uppsala Universitet |
    1000 Förderprogramm Avtal om Läkarutbildning och Forskning
    1000 Fördernummer -
  8. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer LU 1944/3-1
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6434672.rdf
1000 Erstellt am 2022-08-16T15:26:07.763+0200
1000 Erstellt von 280
1000 beschreibt frl:6434672
1000 Bearbeitet von 25
1000 Zuletzt bearbeitet Wed Aug 17 13:36:02 CEST 2022
1000 Objekt bearb. Wed Aug 17 13:31:42 CEST 2022
1000 Vgl. frl:6434672
1000 Oai Id
  1. oai:frl.publisso.de:frl:6434672 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source