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具有临床意义的 CYP2C8*3 和 CYP2C9*2 单倍型来自尼安德特人。

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

机构信息

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

Department of Physiology and Pharmacology, Karolinska Institutet, SE-17177, Stockholm, Sweden.

出版信息

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

DOI:10.1038/s41397-022-00284-6
PMID:35780191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9363273/
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 CYP2C83 and CYP2C92 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.

摘要

基因编码细胞色素 P450 酶的遗传变异影响药物和内源性化合物的代谢。位于染色体 10 上的细胞色素基因 CYP2C8 和 CYP2C9 位点在 CYP2C83 和 CYP2C92 等位基因之间表现出连锁不平衡，形成约 300 千碱基的单倍型。这种单倍型与几种药物的代谢改变有关，最显著的是华法林和苯妥英的代谢减少，导致在其他治疗剂量下出现毒性。在这里，我们表明这种单倍型是从尼安德特人那里遗传下来的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/9363273/b0e32c9b0859/41397_2022_284_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/9363273/b0e32c9b0859/41397_2022_284_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/9363273/b0e32c9b0859/41397_2022_284_Fig1_HTML.jpg

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