The clinically relevant CYP2C8*3 and CYP2C9*2 haplotype is inherited from Neandertals
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作者:
Sigrid Haeggström
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机构:Karolinska Institutet,Department of Neuroscience
Sigrid Haeggström
Magnus Ingelman-Sundberg
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机构:Karolinska Institutet,Department of Neuroscience
Magnus Ingelman-Sundberg
Svante Pääbo
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机构:Karolinska Institutet,Department of Neuroscience
Svante Pääbo
Hugo Zeberg
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机构:Karolinska Institutet,Department of Neuroscience
Hugo Zeberg
机构:
[1] Karolinska Institutet,Department of Neuroscience
[2] Karolinska Institutet,Department of Physiology and Pharmacology
[3] Max Planck Institute for Evolutionary Anthropology,Department of Evolutionary Genetics
[4] Okinawa Institute of Science and Technology,Human Evolutionary Genomics Unit
来源:
The Pharmacogenomics Journal
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2022年
/
22卷
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摘要:
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.
机构:
Childrens Mercy Kansas City, Ctr Genom Med, Kansas City, MO USA
Univ Missouri, Sch Med, Kansas City, MO 64108 USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA
Farrow, Emily G.
Gonzaludo, Nina
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机构:
Illumina Inc, Med Genom Res, San Diego, CA USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA
Gonzaludo, Nina
Halpern, Aaron L.
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机构:
Illumina Inc, Med Genom Res, San Diego, CA USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA
Halpern, Aaron L.
Nickerson, Deborah A.
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h-index: 0
机构:
Univ Washington, Dept Genome Sci, Seattle, WA 98195 USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA
Nickerson, Deborah A.
Miller, Neil A.
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机构:
Childrens Mercy Kansas City, Ctr Genom Med, Kansas City, MO USA
Univ Missouri, Sch Med, Kansas City, MO 64108 USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA
Miller, Neil A.
Pratt, Victoria M.
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机构:
Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA
Pratt, Victoria M.
Kalman, Lisa, V
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h-index: 0
机构:
Ctr Dis Control & Prevent, Informat & Data Sci Branch, Div Lab Syst, Atlanta, GA 30333 USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA
机构:
Childrens Mercy Kansas City, Ctr Genom Med, Kansas City, MO USA
Univ Missouri, Sch Med, Kansas City, MO 64108 USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA
Farrow, Emily G.
Gonzaludo, Nina
论文数: 0引用数: 0
h-index: 0
机构:
Illumina Inc, Med Genom Res, San Diego, CA USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA
Gonzaludo, Nina
Halpern, Aaron L.
论文数: 0引用数: 0
h-index: 0
机构:
Illumina Inc, Med Genom Res, San Diego, CA USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA
Halpern, Aaron L.
Nickerson, Deborah A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Washington, Dept Genome Sci, Seattle, WA 98195 USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA
Nickerson, Deborah A.
Miller, Neil A.
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Mercy Kansas City, Ctr Genom Med, Kansas City, MO USA
Univ Missouri, Sch Med, Kansas City, MO 64108 USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA
Miller, Neil A.
Pratt, Victoria M.
论文数: 0引用数: 0
h-index: 0
机构:
Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA
Pratt, Victoria M.
Kalman, Lisa, V
论文数: 0引用数: 0
h-index: 0
机构:
Ctr Dis Control & Prevent, Informat & Data Sci Branch, Div Lab Syst, Atlanta, GA 30333 USAChildrens Mercy Kansas City, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO USA