The clinically relevant CYP2C8*3 and CYP2C9*2 haplotype is inherited from Neandertals.

Animals Aryl Hydrocarbon Hydroxylases / genetics Cytochrome P-450 CYP2C8 / genetics Cytochrome P-450 CYP2C9 / genetics Gene Frequency Haplotypes / genetics Humans Neanderthals / genetics

Journal

The pharmacogenomics journal
ISSN: 1473-1150
Titre abrégé: Pharmacogenomics J
Pays: United States
ID NLM: 101083949

Informations de publication

Date de publication:
07 2022
Historique:
received: 03 03 2022
accepted: 10 06 2022
revised: 13 05 2022
pubmed: 3 7 2022
medline: 12 8 2022
entrez: 2 7 2022
Statut: ppublish

Résumé

Genetic variation in genes encoding cytochrome P450 enzymes influences the metabolism of drugs and endogenous compounds. The locus containing the cytochrome genes CYP2C8 and CYP2C9 on chromosome 10 exhibits linkage disequilibrium between the CYP2C8*3 and CYP2C9*2 alleles, forming a haplotype of ~300 kilobases. This haplotype is associated with altered metabolism of several drugs, most notably reduced metabolism of warfarin and phenytoin, leading to toxicity at otherwise therapeutic doses. Here we show that this haplotype is inherited from Neandertals.

Identifiants

DOI: 10.1038/s41397-022-00284-6 PMID: 35780191 PMC: PMC9363273
pubmed: 35780191
doi: 10.1038/s41397-022-00284-6
pii: 10.1038/s41397-022-00284-6
pmc: PMC9363273
doi:

Substances chimiques

CYP2C9 protein, human EC 1.14.13.-
Cytochrome P-450 CYP2C9 EC 1.14.13.-
Aryl Hydrocarbon Hydroxylases EC 1.14.14.1
CYP2C8 protein, human EC 1.14.14.1
Cytochrome P-450 CYP2C8 EC 1.14.14.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

247-249

Informations de copyright

© 2022. The Author(s).

Références

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Auteurs

Sigrid Haeggström (S)

Department of Neuroscience, Karolinska Institutet, SE-17177, Stockholm, Sweden.

Magnus Ingelman-Sundberg (M)

Department of Physiology and Pharmacology, Karolinska Institutet, SE-17177, Stockholm, Sweden.
ORCID: 0000-0002-7255-9079

Svante Pääbo (S)

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103, Leipzig, Germany.
Human Evolutionary Genomics Unit, Okinawa Institute of Science and Technology, Okinawa, 904-0495, Japan.

Hugo Zeberg (H)

Department of Neuroscience, Karolinska Institutet, SE-17177, Stockholm, Sweden. hugo.zeberg@ki.se.
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103, Leipzig, Germany. hugo.zeberg@ki.se.
ORCID: 0000-0001-7118-1249

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › The clinically relevant CYP2C8*3 and CYP2C9*2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Hémoprotéines › Cytochromes › Cytochrome P-450 enzyme system › Aryl hydrocarbon hydroxylases › The clinically relevant CYP2C8*3 and CYP2C9*2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Hémoprotéines › Cytochromes › Cytochrome P-450 enzyme system › Famille-2 de cytochromes P450 › Cytochrome P-450 CYP2C8 › The clinically relevant CYP2C8*3 and CYP2C9*2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Hémoprotéines › Cytochromes › Cytochrome P-450 enzyme system › Famille-2 de cytochromes P450 › Limonène hydroxylases › Cytochrome P-450 CYP2C9 › The clinically relevant CYP2C8*3 and CYP2C9*2...
questionsmedicales.fr › Phénomènes génétiques › Fréquence d'allèle › The clinically relevant CYP2C8*3 and CYP2C9*2...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Haplotypes › The clinically relevant CYP2C8*3 and CYP2C9*2...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The clinically relevant CYP2C8*3 and CYP2C9*2...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Néandertaliens › The clinically relevant CYP2C8*3 and CYP2C9*2...