The clinically relevant CYP2C83 and CYP2C92 haplotype is inherited from Neandertals

The clinically relevant CYP2C83 and CYP2C92 haplotype is inherited from Neandertals

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...

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Veröffentlicht in:The pharmacogenomics journal 2022-07, Vol.22 (4), p.247-249
Hauptverfasser: Haeggström, Sigrid, Ingelman-Sundberg, Magnus, Pääbo, Svante, Zeberg, Hugo
Format: Artikel
Sprache:eng
Schlagworte:
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Biomedical and Life Sciences
Biomedicine
Chromosome 10
Clinical medicine
Cytochrome
Cytochrome P450
Drug dosages
Drug metabolism
Enzymes
Gene Expression
Genes
Genetic diversity
Genomes
Haplotypes
Hominids
Human Genetics
Linkage disequilibrium
Metabolism
Nonsteroidal anti-inflammatory drugs
Oncology
Pharmacotherapy
Phenytoin
Population
Psychopharmacology
Toxicity
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Zusammenfassung: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.
ISSN:1470-269X
1473-1150
DOI:10.1038/s41397-022-00284-6