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Characterization of Novel CYP2D6 Alleles across Sub-Saharan African Populations

The CYP2D6 gene has been widely studied to characterize variants and/or star alleles, which account for a significant portion of variability in drug responses observed within and between populations. However, African populations remain under-represented in these studies. The increasing availability...

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Autores principales: Wang, Wendy Y., Twesigomwe, David, Nofziger, Charity, Turner, Amy J., Helmecke, Lena-Sophie, Broeckel, Ulrich, Derezinski, Ashley D., Hazelhurst, Scott, Gaedigk, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605556/
https://www.ncbi.nlm.nih.gov/pubmed/36294714
http://dx.doi.org/10.3390/jpm12101575
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author Wang, Wendy Y.
Twesigomwe, David
Nofziger, Charity
Turner, Amy J.
Helmecke, Lena-Sophie
Broeckel, Ulrich
Derezinski, Ashley D.
Hazelhurst, Scott
Gaedigk, Andrea
author_facet Wang, Wendy Y.
Twesigomwe, David
Nofziger, Charity
Turner, Amy J.
Helmecke, Lena-Sophie
Broeckel, Ulrich
Derezinski, Ashley D.
Hazelhurst, Scott
Gaedigk, Andrea
author_sort Wang, Wendy Y.
collection PubMed
description The CYP2D6 gene has been widely studied to characterize variants and/or star alleles, which account for a significant portion of variability in drug responses observed within and between populations. However, African populations remain under-represented in these studies. The increasing availability of high coverage genomes from African populations has provided the opportunity to fill this knowledge gap. In this study, we characterized computationally predicted novel CYP2D6 star alleles in 30 African subjects for whom DNA samples were available from the Coriell Institute. CYP2D6 genotyping and resequencing was performed using a variety of commercially available and laboratory-developed tests in a collaborative effort involving three laboratories. Fourteen novel CYP2D6 alleles and multiple novel suballeles were identified. This work adds to the growing catalogue of validated African ancestry CYP2D6 allelic variation in pharmacogenomic databases, thus laying the foundation for future functional studies and improving the accuracy of CYP2D6 genotyping, phenotype prediction, and the refinement of clinical pharmacogenomic implementation guidelines in African and global settings.
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spelling pubmed-96055562022-10-27 Characterization of Novel CYP2D6 Alleles across Sub-Saharan African Populations Wang, Wendy Y. Twesigomwe, David Nofziger, Charity Turner, Amy J. Helmecke, Lena-Sophie Broeckel, Ulrich Derezinski, Ashley D. Hazelhurst, Scott Gaedigk, Andrea J Pers Med Article The CYP2D6 gene has been widely studied to characterize variants and/or star alleles, which account for a significant portion of variability in drug responses observed within and between populations. However, African populations remain under-represented in these studies. The increasing availability of high coverage genomes from African populations has provided the opportunity to fill this knowledge gap. In this study, we characterized computationally predicted novel CYP2D6 star alleles in 30 African subjects for whom DNA samples were available from the Coriell Institute. CYP2D6 genotyping and resequencing was performed using a variety of commercially available and laboratory-developed tests in a collaborative effort involving three laboratories. Fourteen novel CYP2D6 alleles and multiple novel suballeles were identified. This work adds to the growing catalogue of validated African ancestry CYP2D6 allelic variation in pharmacogenomic databases, thus laying the foundation for future functional studies and improving the accuracy of CYP2D6 genotyping, phenotype prediction, and the refinement of clinical pharmacogenomic implementation guidelines in African and global settings. MDPI 2022-09-24 /pmc/articles/PMC9605556/ /pubmed/36294714 http://dx.doi.org/10.3390/jpm12101575 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Wendy Y.
Twesigomwe, David
Nofziger, Charity
Turner, Amy J.
Helmecke, Lena-Sophie
Broeckel, Ulrich
Derezinski, Ashley D.
Hazelhurst, Scott
Gaedigk, Andrea
Characterization of Novel CYP2D6 Alleles across Sub-Saharan African Populations
title Characterization of Novel CYP2D6 Alleles across Sub-Saharan African Populations
title_full Characterization of Novel CYP2D6 Alleles across Sub-Saharan African Populations
title_fullStr Characterization of Novel CYP2D6 Alleles across Sub-Saharan African Populations
title_full_unstemmed Characterization of Novel CYP2D6 Alleles across Sub-Saharan African Populations
title_short Characterization of Novel CYP2D6 Alleles across Sub-Saharan African Populations
title_sort characterization of novel cyp2d6 alleles across sub-saharan african populations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605556/
https://www.ncbi.nlm.nih.gov/pubmed/36294714
http://dx.doi.org/10.3390/jpm12101575
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