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.
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Hokkaido Pharmaceut Univ, Sch Pharm, Div Clin Pharmacol, Teine Ku, 15-4-1 Maeda 7 Jo, Sapporo, Hokkaido 0068590, JapanHokkaido Pharmaceut Univ, Sch Pharm, Div Clin Pharmacol, Teine Ku, 15-4-1 Maeda 7 Jo, Sapporo, Hokkaido 0068590, Japan
Kato, Yuka
Mukai, Yuji
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Hokkaido Pharmaceut Univ, Sch Pharm, Div Clin Pharmacol, Teine Ku, 15-4-1 Maeda 7 Jo, Sapporo, Hokkaido 0068590, JapanHokkaido Pharmaceut Univ, Sch Pharm, Div Clin Pharmacol, Teine Ku, 15-4-1 Maeda 7 Jo, Sapporo, Hokkaido 0068590, Japan
Mukai, Yuji
Rane, Anders
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Karolinska Univ Hosp, Karolinska Inst, Dept Lab Med, Div Clin Pharmacol, SE-14186 Stockholm, SwedenHokkaido Pharmaceut Univ, Sch Pharm, Div Clin Pharmacol, Teine Ku, 15-4-1 Maeda 7 Jo, Sapporo, Hokkaido 0068590, Japan
Rane, Anders
Inotsume, Nobuo
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Hokkaido Pharmaceut Univ, Sch Pharm, Div Clin Pharmacol, Teine Ku, 15-4-1 Maeda 7 Jo, Sapporo, Hokkaido 0068590, JapanHokkaido Pharmaceut Univ, Sch Pharm, Div Clin Pharmacol, Teine Ku, 15-4-1 Maeda 7 Jo, Sapporo, Hokkaido 0068590, Japan
Inotsume, Nobuo
Toda, Takaki
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Hokkaido Pharmaceut Univ, Sch Pharm, Div Clin Pharmacol, Teine Ku, 15-4-1 Maeda 7 Jo, Sapporo, Hokkaido 0068590, JapanHokkaido Pharmaceut Univ, Sch Pharm, Div Clin Pharmacol, Teine Ku, 15-4-1 Maeda 7 Jo, Sapporo, Hokkaido 0068590, Japan
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Univ Nacl Autonoma Mexico, Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 04510, DF, MexicoUniv Nacl Autonoma Mexico, Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 04510, DF, Mexico
Sanchez-Pozos, Katy
Rivera-Santiago, Carolina
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Univ Nacl Autonoma Mexico, Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 04510, DF, MexicoUniv Nacl Autonoma Mexico, Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 04510, DF, Mexico
Rivera-Santiago, Carolina
Helena Garcia-Rodriguez, Maria
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Univ Nacl Autonoma Mexico, Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 04510, DF, MexicoUniv Nacl Autonoma Mexico, Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 04510, DF, Mexico
Helena Garcia-Rodriguez, Maria
Guadalupe Ortiz-Lopez, Maria
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Hosp Juarez Mexico, Lab Endocrinol Mol, Mexico City, DF, MexicoUniv Nacl Autonoma Mexico, Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 04510, DF, Mexico
Guadalupe Ortiz-Lopez, Maria
Itzel Pena-Espinoza, Barbara
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UNAM Yucatan PC&TY, Unidad Acad Ciencias & Tecnol, Fac Quim, Lab Diabet, Merida, Yucatan, VenezuelaUniv Nacl Autonoma Mexico, Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 04510, DF, Mexico
Itzel Pena-Espinoza, Barbara
de los Angeles Granados-Silvestre, Maria
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Univ Nacl Autonoma Mexico, Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 04510, DF, MexicoUniv Nacl Autonoma Mexico, Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 04510, DF, Mexico
de los Angeles Granados-Silvestre, Maria
Llerena, Adrian
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Hosp Univ Infanta Cristina, SES, Ctr Invest Clin, Area Salud Badajoz, Badajoz, SpainUniv Nacl Autonoma Mexico, Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 04510, DF, Mexico
Llerena, Adrian
Menjivar, Marta
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Univ Nacl Autonoma Mexico, Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 04510, DF, MexicoUniv Nacl Autonoma Mexico, Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 04510, DF, Mexico