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

Pharmacogenomics J. 2022 Jul;22(4):247-249. doi: 10.1038/s41397-022-00284-6. Epub 2022 Jul 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C8 protein, human
  • Cytochrome P-450 CYP2C8