期刊
PHARMACOGENOMICS JOURNAL
卷 22, 期 4, 页码 247-249出版社
SPRINGERNATURE
DOI: 10.1038/s41397-022-00284-6
关键词
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资金
- Max Planck Society
- NOMIS foundation
- Swedish Research Council [2021-03050, 2021-02732]
- Emil och Wera Cornells Stiftelse
- Stiftelsen Clas Groschinskys Minnesfond
- Jeanssons Stiftelser
- Magnus Bergvalls stiftelse
- Karolinska Institutet
- Swedish Research Council [2021-02732, 2021-03050] Funding Source: Swedish Research Council
Genetic variation in genes encoding cytochrome P450 enzymes affects the metabolism of drugs and endogenous compounds. The locus on chromosome 10 containing the cytochrome genes CYP2C8 and CYP2C9 shows linkage disequilibrium between the CYP2C8*3 and CYP2C9*2 alleles, resulting in a haplotype associated with altered drug metabolism. We demonstrate that this haplotype is inherited from Neanderthals and plays a significant role in the metabolism of warfarin and phenytoin.
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 similar to 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.
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