CYP2D6 and CYP2C19 Genes Associated with Tricontinental and Latin American Ancestry of Peruvians

Alvarado, A.T.; Muñoz, A.M.; Loja, B.; Miyasato, J.M.; García, J.A.; Cerro, R.A.; Quiñones, L.A.; Varela, N.M. Study of the allelic variants CYP2C9*2 and CYP2C9*3 in samples of the Peruvian mestizo population. Biomédica, 2019, 39(3), 601-610.
[http://dx.doi.org/10.7705/biomedica.4636] [PMID: 31584773]

Alvarado, A.T.; Paredes, G.; García, G.; Morales, A.; Muñoz, A.M.; Saravia, M.; Losno, R.; Bendezú, M.R.; Chávez, H.; García, J.A.; Pineda, M.; Sullón-Dextre, L. Serum monitoring of carbamazepine in patients with epilepsy and clinical implications. Pharmacia, 2022, 69(2), 401-406.
[http://dx.doi.org/10.3897/pharmacia.69.e82425]

Rodrigues-Soares, F.; Peñas-Lledó, E.M.; Tarazona-Santos, E.; Sosa-Macías, M.; Terán, E.; López-López, M.; Rodeiro, I.; Moya, G.E.; Calzadilla, L.R.; Ramírez-Roa, R.; Grazina, M.; Estévez-Carrizo, F.E.; Barrantes, R.; LLerena, A.; Tinoco, C.A.; Álvárez, M.; Borbón, A.; Céspedes-Garro, C.; Cobaleda, J.; Andrés, F.; Delgado, R.; Dorado, P.; Fariñas, H.; Ferreiro, V.; Fricke-Galindo, I.; Galaviz-Hernández, C.; Garza-Ocañas, L.; Gilman, R.H.; Hernández, F.; Jiménez-Arce, G.; Jung-Cook, H.; Lares-Aseff, I.; Lazalde-Ramos, B.P.; Michelin, L.; Monroy-Jaramillo, N.; Naranjo, M.E.G.; Ortega-Vázquez, A.; Ortiz-López, R.; Pérez, B.; Pérez-Páramo, Y.X.; Remirez, D.; Rojas-Martínez, A.; Sarmiento, A.P.; Scliar, M.; Terán, S.; Zamudio, R. Genomic ancestry, CYP 2D6,CYP 2C9, andCYP 2C19 among latin Americans. Clin. Pharmacol. Ther., 2020, 107(1), 257-268.
[http://dx.doi.org/10.1002/cpt.1598] [PMID: 31376146]

Kane, M. CYP2D6 Overview: Allele and phenotype frequencies. Medical Genetics Summaries. 2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK574601/

Zanger, U.M.; Raimundo, S.; Eichelbaum, M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch. Pharmacol., 2004, 369(1), 23-37.
[http://dx.doi.org/10.1007/s00210-003-0832-2] [PMID: 14618296]

ur Rasheed, M.S.; Mishra, A.K.; Singh, M.P. Cytochrome P450 2D6 and Parkinson’s Disease: Polymorphism, metabolic role, risk and protection. Neurochem. Res., 2017, 42(12), 3353-3361.
[http://dx.doi.org/10.1007/s11064-017-2384-8] [PMID: 28871472]

Smith, E.C. Understanding CYP2D6 and its role in tamoxifen metabolism. Oncol. Nurs. Forum, 2013, 40(6), 547-548.
[http://dx.doi.org/10.1188/13.ONF.547-548] [PMID: 24161632]

Gutiérrez Rico, E.M.; Kikuchi, A.; Saito, T.; Kumondai, M.; Hishinuma, E.; Kaneko, A.; Chan, C.W.; Gitaka, J.; Nakayoshi, T.; Oda, A.; Saito, S.; Hirasawa, N.; Hiratsuka, M. CYP2D6 genotyping analysis and functional characterization of novel allelic variants in a Ni-Vanuatu and Kenyan population by assessing dextromethorphan O-demethylation activity. Drug Metab. Pharmacokinet., 2020, 35(1), 89-101.
[http://dx.doi.org/10.1016/j.dmpk.2019.07.003] [PMID: 32037159]

Nguyen, H.H.; Ma, T.T.H.; Vu, N.P.; Bach, Q.T.N.; Vu, T.H.; Nguyen, T.D.; Nong, H.V. Single nucleotide and structural variants of CYP2D6 gene in Kinh Vietnamese population. Medicine (Baltimore), 2019, 98(22), e15891.
[http://dx.doi.org/10.1097/MD.0000000000015891] [PMID: 31145348]

Qiao, W.; Martis, S.; Mendiratta, G.; Shi, L.; Botton, M.R.; Yang, Y.; Gaedigk, A.; Vijzelaar, R.; Edelmann, L.; Kornreich, R.; Desnick, R.J.; Scott, S.A. Integrated CYP2D6 interrogation for multiethnic copy number and tandem allele detection. Pharmacogenomics, 2019, 20(1), 9-20.
[http://dx.doi.org/10.2217/pgs-2018-0135] [PMID: 30730286]

Leitão, L.P.C.; Souza, T.P.; Rodrigues, J.C.G.; Fernandes, M.R.; Santos, S.; Santos, N.P.C. The metabolization profile of the CYP2D6 Gene in Amerindian populations: A review. Genes (Basel), 2020, 11(3), 262.
[http://dx.doi.org/10.3390/genes11030262] [PMID: 32121156]

Alvarado, A.T.; Ybañez-Julca, R.; Muñoz, A.M.; Tejada-Bechi, C.; Cerro, R.; Quiñones, L.A.; Varela, N.; Alvarado, C.A.; Alvarado, E.; Bendezú, M.R.; García, J.A. Frequency of CYP2D6*3 and *4 and metabolizer phenotypes in three mestizo Peruvian populations. Pharmacia, 2021, 68(4), 891-898.
[http://dx.doi.org/10.3897/pharmacia.68.e75165]

Johansson, I.; Ingelman-Sundberg, M. Genetic polymorphism and toxicology--with emphasis on cytochrome p450. Toxicol. Sci., 2011, 120(1), 1-13.
[http://dx.doi.org/10.1093/toxsci/kfq374] [PMID: 21149643]

Flores-Angulo, C.; Villegas, C.; Mora, Y.; Martínez, J.A.; Oropeza, T.; Moreno, N. Variantes alélicas de CYP2D6: *4, *6 y *10 en una muestra de residentes del estado Aragua, Venezuela. Rev. Peru. Med. Exp. Salud Publica, 2015, 32(4), 746-751.
[http://dx.doi.org/10.17843/rpmesp.2015.324.1767] [PMID: 26732924]

Kagimoto, M.; Heim, M.; Kagimoto, K.; Zeugin, T.; Meyer, U.A. Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes. J. Biol. Chem., 1990, 265(28), 17209-17214.
[http://dx.doi.org/10.1016/S0021-9258(17)44890-3] [PMID: 2211621]

Dorado, P.; González, I.; Naranjo, M.E.G.; de Andrés, F.; Peñas-Lledó, E.M.; Calzadilla, L.R. LLerena, A. Lessons from Cuba for global precision medicine: CYP2D6 genotype is not a robust predictor of CYP2D6 ultrarapid metabolism. OMICS, 2017, 21(1), 17-26.
[http://dx.doi.org/10.1089/omi.2016.0166] [PMID: 28271978]

Quiñones, L.; Roco, Á.; Cayún, J.P.; Escalante, P.; Miranda, C.; Varela, N.; Meneses, F.; Gallegos, B.; Zaruma-Torres, F.; Lares-Asseff, I. Farmacogenómica como herramienta fundamental para la medicina personalizada: Aplicaciones en la práctica clínica. Rev. Med. Chil., 2017, 145(4), 483-500.
[http://dx.doi.org/10.4067/S0034-98872017000400009] [PMID: 28748996]

Lu, Y.; Mo, C.; Zeng, Z.; Chen, S.; Xie, Y.; Peng, Q.; He, Y.; Deng, Y.; Wang, J.; Xie, L.; Zeng, J.; Li, S.; Qin, X. El polimorfismo del alelo CYP2D6*4 aumenta el riesgo de enfermedad de Parkinson: evidencia de metanálisis. PLoS One, 2013, 8(12), e84413.
[http://dx.doi.org/10.1371/journal.pone.0084413] [PMID: 24376807]

de Andrés, F.; Sosa-Macías, M.; Ramos, B.P.L.; Naranjo, M.E.G. LLerena, A. CYP450 Genotype/phenotype concordance in mexican amerindian indigenous populations–where to from here for global precision medicine? OMICS, 2017, 21(9), 509-519.
[http://dx.doi.org/10.1089/omi.2017.0101] [PMID: 28873029]

Saxena, R.; Shaw, G.L.; Relling, M.V.; Frame, J.N.; Moir, D.T.; Evans, W.E.; Caporaso, N.; Weiffenbach, B. Identification of a new variant CYP2D6 allele with a single base deletion in exon 3 and its association with the poor metabolizer phenotype. Hum. Mol. Genet., 1994, 3(6), 923-926.
[http://dx.doi.org/10.1093/hmg/3.6.923] [PMID: 7951238]

Chen, P.Y.; Wang, S.C.; Poland, R.E.; Lin, K.M. Biological variations in depression and anxiety between East and West. CNS Neurosci. Ther., 2009, 15(3), 283-294.
[http://dx.doi.org/10.1111/j.1755-5949.2009.00093.x] [PMID: 19691548]

Qi, G.; Yin, S.; Zhang, G.; Wang, X. Genetic and epigenetic polymorphisms of eNOS and CYP2D6 in mainland Chinese Tibetan, Mongolian, Uygur, and Han populations. Pharmacogenomics J., 2020, 20(1), 114-125.
[http://dx.doi.org/10.1038/s41397-019-0104-2] [PMID: 31616043]

Gaedigk, A.; Blum, M.; Gaedigk, R.; Eichelbaum, M.; Meyer, U.A. Deletion of the entire cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism. Am. J. Hum. Genet., 1991, 48(5), 943-950.
[PMID: 1673290]

Céspedes-Garro, C.; Rodrigues-Soares, F.; Jiménez-Arce, G.; Naranjo, M.G.; Tarazona-Santos, E.; Fariñas, H.; Barrantes, R.; Llerena, A. Relevance of the ancestry for the variability of the drug-metabolizing enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population. Rev. Biol. Trop., 2016, 64(3), 1067-1076.
[http://dx.doi.org/10.15517/rbt.v64i3.20901] [PMID: 29461783]

Maruf, A.A.; Greenslade, A.; Arnold, P.D.; Bousman, C. Antidepressant pharmacogenetics in children and young adults: A systematic review. J. Affect. Disord., 2019, 254, 98-108.
[http://dx.doi.org/10.1016/j.jad.2019.05.025] [PMID: 31112844]

Taylor, C.; Crosby, I.; Yip, V.; Maguire, P.; Pirmohamed, M.; Turner, R.M. A Review of the Important Role of CYP2D6 in Pharmacogenomics. Genes (Basel), 2020, 11(11), 1295.
[http://dx.doi.org/10.3390/genes11111295] [PMID: 33143137]

Lim, Y.J.; Cha, E.Y.; Jung, H.E.; Ghim, J.L.; Lee, S.J.; Kim, E.Y.; Shin, J.G. Genetic polymorphisms of CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 in Vietnamese-Koreans. Transl. Clin. Pharmacol., 2014, 22(2), 70-77.
[http://dx.doi.org/10.12793/tcp.2014.22.2.70]

Skadrić, I.; Stojković, O. Defining screening panel of functional variants of CYP1A1, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 genes in Serbian population. Int. J. Legal Med., 2020, 134(2), 433-439.
[http://dx.doi.org/10.1007/s00414-019-02234-7] [PMID: 31858263]

Vargas, R.J.; Cobar, O. CYP450 y farmacogenética en Guatemala. Revisión narrativa. Ciencia. Tecnología y Salud, 2021, 8(2), 211-219.
[http://dx.doi.org/10.36829/63CTS.v8i2.947]

Saeed, L.H.; Mayet, A.Y. Genotype-phenotype analysis of CYP2C19 in healthy saudi individuals and its potential clinical implication in drug therapy. Int. J. Med. Sci., 2013, 10(11), 1497-1502.
[http://dx.doi.org/10.7150/ijms.6795] [PMID: 24046523]

Lee, S.J. Clinical application of CYP2C19 pharmacogenetics toward more personalized medicine. Front. Genet., 2013, 3, 318.
[http://dx.doi.org/10.3389/fgene.2012.00318] [PMID: 23378847]

Bousman, C.; Maruf, A.A.; Müller, D.J. Towards the integration of pharmacogenetics in psychiatry. Curr. Opin. Psychiatry, 2019, 32(1), 7-15.
[http://dx.doi.org/10.1097/YCO.0000000000000465] [PMID: 30299306]

Ingelman-Sundberg, M.; Rodríguez-Antona, C. Pharmacogenetics of drug-metabolizing enzymes: implications for a safer and more effective drug therapy. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2005, 360(1460), 1563-1570.
[http://dx.doi.org/10.1098/rstb.2005.1685] [PMID: 16096104]

De, T.; Park, C.S.; Perera, M.A. Cardiovascular pharmacogenomics: does it matter if you’re black or white? Annu. Rev. Pharmacol. Toxicol., 2019, 59(1), 577-603.
[http://dx.doi.org/10.1146/annurev-pharmtox-010818-021154] [PMID: 30296897]

Vílchez, H. Hacia una nueva diversidad: Migraciones asiáticas en América Latina. Tiempo y Espacio, 2016, 26(65), 99-119.

Marsh, S.; King, C.R.; Van Booven, D.J.; Revollo, J.Y.; Gilman, R.H.; McLeod, H.L. Pharmacogenomic assessment of Mexican and Peruvian populations. Pharmacogenomics, 2015, 16(5), 441-448.
[http://dx.doi.org/10.2217/pgs.15.10] [PMID: 25916516]

Sandoval, J.R.; Salazar-Granara, A.; Acosta, O.; Castillo-Herrera, W.; Fujita, R.; Pena, S.D.J.; Santos, F.R. Tracing the genomic ancestry of Peruvians reveals a major legacy of pre-Columbian ancestors. J. Hum. Genet., 2013, 58(9), 627-634.
[http://dx.doi.org/10.1038/jhg.2013.73] [PMID: 23863748]

CIA World Factbook: Peru , 2021. Available from: https://www.cia.gov/the-world-factbook/countries/peru/

Campbell, L. American Indian Languages: The Historical Linguistics of Native America. Oxford Studies in Anthropological Linguistics; Oxford University Press: New York, 1997.

Vera, M. Molecular genetic profile of cytochrome CYP2D6 in patients with tuberculosis treated at the Regional Hospital of Ayacucho-2013 Professional thesis San Cristobal de Huamanga National University: Ayacucho, 2014.

Ortiz, L. Metabolizing phenotypes of the CYP2D6 gene in schizophrenic patients treated with antipsychotic drugs. Ayacucho, professional training school of pharmacy and biochemistry: San Cristóbal de Huamanga National University; Ayacucho, 2017.

Ortiz, L. Distribution of the *4 allele of Cytochrome CYP2D6 in Peruvian subpopulations. [Professional thesis]. National University of San Marcos.: Lima, 2018.

Valdivia, C. Identification of single nucleotide polymorphisms (SNP'S) of cytochrome P450, CYP2C9*2 AND CYP2C19*2 AND *3, in epileptic patients; Catholic University of Santa Maria: Arequipa, 2018.

Tabari, R.G.; Marjani, A.; Ataby, O.A.; Mansourian, A.R.; Samai, N.M. Genetic polymorphism of cytochrome p450 (2C19) enzyme in Iranian Turkman Ethnic Group. Oman Med. J., 2013, 28(4), 237-244.
[http://dx.doi.org/10.5001/omj.2013.69] [PMID: 23904915]

Mirzaev, K.; Zelenskaya, E.; Barbarash, O.; Ganyukov, V.; Apartsin, K.; Saraeva, N.; Nikolaev, K.; Ryzhikova, K.; Lifshits, G.; Sychev, D. CYP2C19 polymorphism frequency in Russian patients in Central Russia and Siberia with acute coronary syndrome. Pharm. Genomics Pers. Med., 2017, 10, 107-114.
[http://dx.doi.org/10.2147/PGPM.S126305] [PMID: 28442925]

Menoyo, A.; del Rio, E.; Baiget, M. Characterization of variant alleles of cytochrome CYP2D6 in a Spanish population. Cell Biochem. Funct., 2006, 24(5), 381-385.
[http://dx.doi.org/10.1002/cbf.1258] [PMID: 16130179]

Wang, T.; Zhao, T.; Bao, S.; Jia, L.; Feng, J.; Yu, A.; Sun, L.; Guo, X.; Li, H.; Yu, L. CYP2C19, PON1, and ABCB1 gene polymorphisms in Han and Uygur populations with coronary artery disease in Northwestern Xinjiang, China, From 2014 Through 2019. Medicine (Baltimore), 2020, 99(29), e20582.
[http://dx.doi.org/10.1097/MD.0000000000020582] [PMID: 32702814]

Biswas, M. Global distribution of CYP2C19 risk phenotypes affecting safety and effectiveness of medications. Pharmacogenom J., 2021, 21(2), 190-199.
[http://dx.doi.org/10.1038/s41397-020-00196-3] [PMID: 33082528]

Naranjo, M.G.; Rodrigues-Soares, F.; Peñas-Lledó, E.M.; Tarazona-Santos, E.; Fariñas, H.; Rodeiro, I.; Terán, E.; Grazina, M.; Moya, G.E.; López-López, M.; Sarmiento, A.P.; Calzadilla, L.R.; Ramírez-Roa, R.; Ortiz-López, R.; Estévez-Carrizo, F.E.; Sosa-Macías, M.; Barrantes, R. LLerena, A. Interethnic variability in CYP2D6, CYP2C9, and CYP2C19 genes and predicted drug metabolism phenotypes among 6060 Ibero- and Native Americans: RIBEF-CEIBA consortium report on population pharmacogenomics. OMICS, 2018, 22(9), 575-588.
[http://dx.doi.org/10.1089/omi.2018.0114] [PMID: 30183544]

Auton, A.; Abecasis, G.R.; Altshuler, D.M.; Durbin, R.M.; Abecasis, G.R.; Bentley, D.R.; Chakravarti, A.; Clark, A.G.; Donnelly, P.; Eichler, E.E.; Flicek, P.; Gabriel, S.B.; Gibbs, R.A.; Green, E.D.; Hurles, M.E.; Knoppers, B.M.; Korbel, J.O.; Lander, E.S.; Lee, C.; Lehrach, H.; Mardis, E.R.; Marth, G.T.; McVean, G.A.; Nickerson, D.A.; Schmidt, J.P.; Sherry, S.T.; Wang, J.; Wilson, R.K.; Gibbs, R.A.; Boerwinkle, E.; Doddapaneni, H.; Han, Y.; Korchina, V.; Kovar, C.; Lee, S.; Muzny, D.; Reid, J.G.; Zhu, Y.; Wang, J.; Chang, Y.; Feng, Q.; Fang, X.; Guo, X.; Jian, M.; Jiang, H.; Jin, X.; Lan, T.; Li, G.; Li, J.; Li, Y.; Liu, S.; Liu, X.; Lu, Y.; Ma, X.; Tang, M.; Wang, B.; Wang, G.; Wu, H.; Wu, R.; Xu, X.; Yin, Y.; Zhang, D.; Zhang, W.; Zhao, J.; Zhao, M.; Zheng, X.; Lander, E.S.; Altshuler, D.M.; Gabriel, S.B.; Gupta, N.; Gharani, N.; Toji, L.H.; Gerry, N.P.; Resch, A.M.; Flicek, P.; Barker, J.; Clarke, L.; Gil, L.; Hunt, S.E.; Kelman, G.; Kulesha, E.; Leinonen, R.; McLaren, W.M.; Radhakrishnan, R.; Roa, A.; Smirnov, D.; Smith, R.E.; Streeter, I.; Thormann, A.; Toneva, I.; Vaughan, B.; Zheng-Bradley, X.; Bentley, D.R.; Grocock, R.; Humphray, S.; James, T.; Kingsbury, Z.; Lehrach, H.; Sudbrak, R.; Albrecht, M.W.; Amstislavskiy, V.S.; Borodina, T.A.; Lienhard, M.; Mertes, F.; Sultan, M.; Timmermann, B.; Yaspo, M-L.; Mardis, E.R.; Wilson, R.K.; Fulton, L.; Fulton, R.; Sherry, S.T.; Ananiev, V.; Belaia, Z.; Beloslyudtsev, D.; Bouk, N.; Chen, C.; Church, D.; Cohen, R.; Cook, C.; Garner, J.; Hefferon, T.; Kimelman, M.; Liu, C.; Lopez, J.; Meric, P.; O’Sullivan, C.; Ostapchuk, Y.; Phan, L.; Ponomarov, S.; Schneider, V.; Shekhtman, E.; Sirotkin, K.; Slotta, D.; Zhang, H.; McVean, G.A.; Durbin, R.M.; Balasubramaniam, S.; Burton, J.; Danecek, P.; Keane, T.M.; Kolb-Kokocinski, A.; McCarthy, S.; Stalker, J.; Quail, M.; Schmidt, J.P.; Davies, C.J.; Gollub, J.; Webster, T.; Wong, B.; Zhan, Y.; Auton, A.; Campbell, C.L.; Kong, Y.; Marcketta, A.; Gibbs, R.A.; Yu, F.; Antunes, L.; Bainbridge, M.; Muzny, D.; Sabo, A.; Huang, Z.; Wang, J.; Coin, L.J.M.; Fang, L.; Guo, X.; Jin, X.; Li, G.; Li, Q.; Li, Y.; Li, Z.; Lin, H.; Liu, B.; Luo, R.; Shao, H.; Xie, Y.; Ye, C.; Yu, C.; Zhang, F.; Zheng, H.; Zhu, H.; Alkan, C.; Dal, E.; Kahveci, F.; Marth, G.T.; Garrison, E.P.; Kural, D.; Lee, W-P.; Fung Leong, W.; Stromberg, M.; Ward, A.N.; Wu, J.; Zhang, M.; Daly, M.J.; DePristo, M.A.; Handsaker, R.E.; Altshuler, D.M.; Banks, E.; Bhatia, G.; del Angel, G.; Gabriel, S.B.; Genovese, G.; Gupta, N.; Li, H.; Kashin, S.; Lander, E.S.; McCarroll, S.A.; Nemesh, J.C.; Poplin, R.E.; Yoon, S.C.; Lihm, J.; Makarov, V.; Clark, A.G.; Gottipati, S.; Keinan, A.; Rodriguez-Flores, J.L.; Korbel, J.O.; Rausch, T.; Fritz, M.H.; Stütz, A.M.; Flicek, P.; Beal, K.; Clarke, L.; Datta, A.; Herrero, J.; McLaren, W.M.; Ritchie, G.R.S.; Smith, R.E.; Zerbino, D.; Zheng-Bradley, X.; Sabeti, P.C.; Shlyakhter, I.; Schaffner, S.F.; Vitti, J.; Cooper, D.N.; Ball, E.V.; Stenson, P.D.; Bentley, D.R.; Barnes, B.; Bauer, M.; Keira Cheetham, R.; Cox, A.; Eberle, M.; Humphray, S.; Kahn, S.; Murray, L.; Peden, J.; Shaw, R.; Kenny, E.E.; Batzer, M.A.; Konkel, M.K.; Walker, J.A.; MacArthur, D.G.; Lek, M.; Sudbrak, R.; Amstislavskiy, V.S.; Herwig, R.; Mardis, E.R.; Ding, L.; Koboldt, D.C.; Larson, D.; Ye, K.; Gravel, S.; Swaroop, A.; Chew, E.; Lappalainen, T.; Erlich, Y.; Gymrek, M.; Frederick Willems, T.; Simpson, J.T.; Shriver, M.D.; Rosenfeld, J.A.; Bustamante, C.D.; Montgomery, S.B.; De La Vega, F.M.; Byrnes, J.K.; Carroll, A.W.; DeGorter, M.K.; Lacroute, P.; Maples, B.K.; Martin, A.R.; Moreno-Estrada, A.; Shringarpure, S.S.; Zakharia, F.; Halperin, E.; Baran, Y.; Lee, C.; Cerveira, E.; Hwang, J.; Malhotra, A.; Plewczynski, D.; Radew, K.; Romanovitch, M.; Zhang, C.; Hyland, F.C.L.; Craig, D.W.; Christoforides, A.; Homer, N.; Izatt, T.; Kurdoglu, A.A.; Sinari, S.A.; Squire, K.; Sherry, S.T.; Xiao, C.; Sebat, J.; Antaki, D.; Gujral, M.; Noor, A.; Ye, K.; Burchard, E.G.; Hernandez, R.D.; Gignoux, C.R.; Haussler, D.; Katzman, S.J.; James Kent, W.; Howie, B.; Ruiz-Linares, A.; Dermitzakis, E.T.; Devine, S.E.; Abecasis, G.R.; Min Kang, H.; Kidd, J.M.; Blackwell, T.; Caron, S.; Chen, W.; Emery, S.; Fritsche, L.; Fuchsberger, C.; Jun, G.; Li, B.; Lyons, R.; Scheller, C.; Sidore, C.; Song, S.; Sliwerska, E.; Taliun, D.; Tan, A.; Welch, R.; Kate Wing, M.; Zhan, X.; Awadalla, P.; Hodgkinson, A.; Li, Y.; Shi, X.; Quitadamo, A.; Lunter, G.; McVean, G.A.; Marchini, J.L.; Myers, S.; Churchhouse, C.; Delaneau, O.; Gupta-Hinch, A.; Kretzschmar, W.; Iqbal, Z.; Mathieson, I.; Menelaou, A.; Rimmer, A.; Xifara, D.K.; Oleksyk, T.K.; Fu, Y.; Liu, X.; Xiong, M.; Jorde, L.; Witherspoon, D.; Xing, J.; Eichler, E.E.; Browning, B.L.; Browning, S.R.; Hormozdiari, F.; Sudmant, P.H.; Khurana, E.; Durbin, R.M.; Hurles, M.E.; Tyler-Smith, C.; Albers, C.A.; Ayub, Q.; Balasubramaniam, S.; Chen, Y.; Colonna, V.; Danecek, P.; Jostins, L.; Keane, T.M.; McCarthy, S.; Walter, K.; Xue, Y.; Gerstein, M.B.; Abyzov, A.; Balasubramanian, S.; Chen, J.; Clarke, D.; Fu, Y.; Harmanci, A.O.; Jin, M.; Lee, D.; Liu, J.; Jasmine Mu, X.; Zhang, J.; Zhang, Y.; Li, Y.; Luo, R.; Zhu, H.; Alkan, C.; Dal, E.; Kahveci, F.; Marth, G.T.; Garrison, E.P.; Kural, D.; Lee, W-P.; Ward, A.N.; Wu, J.; Zhang, M.; McCarroll, S.A.; Handsaker, R.E.; Altshuler, D.M.; Banks, E.; del Angel, G.; Genovese, G.; Hartl, C.; Li, H.; Kashin, S.; Nemesh, J.C.; Shakir, K.; Yoon, S.C.; Lihm, J.; Makarov, V.; Degenhardt, J.; Korbel, J.O.; Fritz, M.H.; Meiers, S.; Raeder, B.; Rausch, T.; Stütz, A.M.; Flicek, P.; Paolo Casale, F.; Clarke, L.; Smith, R.E.; Stegle, O.; Zheng-Bradley, X.; Bentley, D.R.; Barnes, B.; Keira Cheetham, R.; Eberle, M.; Humphray, S.; Kahn, S.; Murray, L.; Shaw, R.; Lameijer, E-W.; Batzer, M.A.; Konkel, M.K.; Walker, J.A.; Ding, L.; Hall, I.; Ye, K.; Lacroute, P.; Lee, C.; Cerveira, E.; Malhotra, A.; Hwang, J.; Plewczynski, D.; Radew, K.; Romanovitch, M.; Zhang, C.; Craig, D.W.; Homer, N.; Church, D.; Xiao, C.; Sebat, J.; Antaki, D.; Bafna, V.; Michaelson, J.; Ye, K.; Devine, S.E.; Gardner, E.J.; Abecasis, G.R.; Kidd, J.M.; Mills, R.E.; Dayama, G.; Emery, S.; Jun, G.; Shi, X.; Quitadamo, A.; Lunter, G.; McVean, G.A.; Chen, K.; Fan, X.; Chong, Z.; Chen, T.; Witherspoon, D.; Xing, J.; Eichler, E.E.; Chaisson, M.J.; Hormozdiari, F.; Huddleston, J.; Malig, M.; Nelson, B.J.; Sudmant, P.H.; Parrish, N.F.; Khurana, E.; Hurles, M.E.; Blackburne, B.; Lindsay, S.J.; Ning, Z.; Walter, K.; Zhang, Y.; Gerstein, M.B.; Abyzov, A.; Chen, J.; Clarke, D.; Lam, H.; Jasmine Mu, X.; Sisu, C.; Zhang, J.; Zhang, Y.; Gibbs, R.A.; Yu, F.; Bainbridge, M.; Challis, D.; Evani, U.S.; Kovar, C.; Lu, J.; Muzny, D.; Nagaswamy, U.; Reid, J.G.; Sabo, A.; Yu, J.; Guo, X.; Li, W.; Li, Y.; Wu, R.; Marth, G.T.; Garrison, E.P.; Fung Leong, W.; Ward, A.N.; del Angel, G.; DePristo, M.A.; Gabriel, S.B.; Gupta, N.; Hartl, C.; Poplin, R.E.; Clark, A.G.; Rodriguez-Flores, J.L.; Flicek, P.; Clarke, L.; Smith, R.E.; Zheng-Bradley, X.; MacArthur, D.G.; Mardis, E.R.; Fulton, R.; Koboldt, D.C.; Gravel, S.; Bustamante, C.D.; Craig, D.W.; Christoforides, A.; Homer, N.; Izatt, T.; Sherry, S.T.; Xiao, C.; Dermitzakis, E.T.; Abecasis, G.R.; Min Kang, H.; McVean, G.A.; Gerstein, M.B.; Balasubramanian, S.; Habegger, L.; Yu, H.; Flicek, P.; Clarke, L.; Cunningham, F.; Dunham, I.; Zerbino, D.; Zheng-Bradley, X.; Lage, K.; Berg Jespersen, J.; Horn, H.; Montgomery, S.B.; DeGorter, M.K.; Khurana, E.; Tyler-Smith, C.; Chen, Y.; Colonna, V.; Xue, Y.; Gerstein, M.B.; Balasubramanian, S.; Fu, Y.; Kim, D.; Auton, A.; Marcketta, A.; Desalle, R.; Narechania, A.; Wilson Sayres, M.A.; Garrison, E.P.; Handsaker, R.E.; Kashin, S.; McCarroll, S.A.; Rodriguez-Flores, J.L.; Flicek, P.; Clarke, L.; Zheng-Bradley, X.; Erlich, Y.; Gymrek, M.; Frederick Willems, T.; Bustamante, C.D.; Mendez, F.L.; David, P.G.; Underhill, P.A.; Lee, C.; Cerveira, E.; Malhotra, A.; Romanovitch, M.; Zhang, C.; Abecasis, G.R.; Coin, L.; Shao, H.; Mittelman, D.; Tyler-Smith, C.; Ayub, Q.; Banerjee, R.; Cerezo, M.; Chen, Y.; Fitzgerald, T.W.; Louzada, S.; Massaia, A.; McCarthy, S.; Ritchie, G.R.; Xue, Y.; Yang, F.; Gibbs, R.A.; Kovar, C.; Kalra, D.; Hale, W.; Muzny, D.; Reid, J.G.; Wang, J.; Dan, X.; Guo, X.; Li, G.; Li, Y.; Ye, C.; Zheng, X.; Altshuler, D.M.; Flicek, P.; Clarke, L.; Zheng-Bradley, X.; Bentley, D.R.; Cox, A.; Humphray, S.; Kahn, S.; Sudbrak, R.; Albrecht, M.W.; Lienhard, M.; Larson, D.; Craig, D.W.; Izatt, T.; Kurdoglu, A.A.; Sherry, S.T.; Xiao, C.; Haussler, D.; Abecasis, G.R.; McVean, G.A.; Durbin, R.M.; Balasubramaniam, S.; Keane, T.M.; McCarthy, S.; Stalker, J.; Chakravarti, A.; Knoppers, B.M.; Abecasis, G.R.; Barnes, K.C.; Beiswanger, C.; Burchard, E.G.; Bustamante, C.D.; Cai, H.; Cao, H.; Durbin, R.M.; Gerry, N.P.; Gharani, N.; Gibbs, R.A.; Gignoux, C.R.; Gravel, S.; Henn, B.; Jones, D.; Jorde, L.; Kaye, J.S.; Keinan, A.; Kent, A.; Kerasidou, A.; Li, Y.; Mathias, R.; McVean, G.A.; Moreno-Estrada, A.; Ossorio, P.N.; Parker, M.; Resch, A.M.; Rotimi, C.N.; Royal, C.D.; Sandoval, K.; Su, Y.; Sudbrak, R.; Tian, Z.; Tishkoff, S.; Toji, L.H.; Tyler-Smith, C.; Via, M.; Wang, Y.; Yang, H.; Yang, L.; Zhu, J.; Bodmer, W.; Bedoya, G.; Ruiz-Linares, A.; Cai, Z.; Gao, Y.; Chu, J.; Peltonen, L.; Garcia-Montero, A.; Orfao, A.; Dutil, J.; Martinez-Cruzado, J.C.; Oleksyk, T.K.; Barnes, K.C.; Mathias, R.A.; Hennis, A.; Watson, H.; McKenzie, C.; Qadri, F.; LaRocque, R.; Sabeti, P.C.; Zhu, J.; Deng, X.; Sabeti, P.C.; Asogun, D.; Folarin, O.; Happi, C.; Omoniwa, O.; Stremlau, M.; Tariyal, R.; Jallow, M.; Sisay Joof, F.; Corrah, T.; Rockett, K.; Kwiatkowski, D.; Kooner, J.; Tịnh Hiên, T.; Dunstan, S.J.; Thuy Hang, N.; Fonnie, R.; Garry, R.; Kanneh, L.; Moses, L.; Sabeti, P.C.; Schieffelin, J.; Grant, D.S.; Gallo, C.; Poletti, G.; Saleheen, D.; Rasheed, A.; Brooks, L.D.; Felsenfeld, A.L.; McEwen, J.E.; Vaydylevich, Y.; Green, E.D.; Duncanson, A.; Dunn, M.; Schloss, J.A.; Wang, J.; Yang, H.; Auton, A.; Brooks, L.D.; Durbin, R.M.; Garrison, E.P.; Min Kang, H.; Korbel, J.O.; Marchini, J.L.; McCarthy, S.; McVean, G.A.; Abecasis, G.R. A global reference for human genetic variation. Nature, 2015, 526(7571), 68-74.
[http://dx.doi.org/10.1038/nature15393]

Koopmans, A. CYP2D6 and CYP2C19 genotyping in psychiatry: bridging the gap between practice and lab; ProefschriftMaken: Maastricht, 2021.
[http://dx.doi.org/10.26481/dis.20210512ak]

Bravo-Villalta, H.V.; Yamamoto, K.; Nakamura, K.; Bayá, A.; Okada, Y.; Horiuchi, R. Genetic polymorphism of CYP2C9 and CYP2C19 in a Bolivian population: an investigative and comparative study. Eur. J. Clin. Pharmacol., 2005, 61(3), 179-184.
[http://dx.doi.org/10.1007/s00228-004-0890-5] [PMID: 15776277]

Santos, P.C.J.L.; Soares, R.A.G.; Santos, D.B.G.; Nascimento, R.M.; Coelho, G.L.L.M.; Nicolau, J.C.; Mill, J.G.; Krieger, J.E.; Pereira, A.C. CYP2C19 and ABCB1gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population. BMC Med. Genet., 2011, 12(1), 13.
[http://dx.doi.org/10.1186/1471-2350-12-13] [PMID: 21247447]

Salazar-Flores, J.; Torres-Reyes, L.A.; Martínez-Cortés, G.; Rubi-Castellanos, R.; Sosa-Macías, M.; Muñoz-Valle, J.F.; González-González, C.; Ramírez, A.; Román, R.; Méndez, J.L.; Barrera, A.; Torres, A.; Medina, R.; Rangel-Villalobos, H. Distribution of CYP2D6 and CYP2C19 polymorphisms associated with poor metabolizer phenotype in five Amerindian groups and western Mestizos from Mexico. Genet. Test. Mol. Biomarkers, 2012, 16(9), 1098-1104.
[http://dx.doi.org/10.1089/gtmb.2012.0055] [PMID: 22913530]

Favela-Mendoza, A.F.; Martinez-Cortes, G.; Hernandez-Zaragoza, M.; Salazar-Flores, J.; Muñoz-Valle, J.F.; Martinez-Sevilla, V.M.; Velazquez-Suarez, N.Y.; Rangel-Villalobos, H. Genetic variability of CYP2C19 in a Mexican population: contribution to the knowledge of the inheritance pattern of CYP2C19*17 to develop the ultrarapid metabolizer phenotype. J. Genet., 2015, 94(1), 3-7.
[http://dx.doi.org/10.1007/s12041-015-0477-1] [PMID: 25846871]

León-Moreno, L.C.; Saldaña-Cruz, A.M.; Sánchez-Corona, J.; Mendoza-Carrera, F.; García-Zapién, A.G.; Revilla-Monsalve, C.; Islas-Andrade, S.; Brito-Zurita, O.; Pérez-Vargas, A.; Flores-Martínez, S.E. Distribution of potential risk alleles and haplotypes of the CYP2C9 and CYP2C19 genes in Mexican native populations: A comparative study among Amerindian populations. Meta Gene, 2019, 20, 100565.
[http://dx.doi.org/10.1016/j.mgene.2019.100565]

Hernandez-Suarez, D.; Tomassini-Fernandini, J.; Cuevas, A.; Rosario-Berrios, A.; Nuñez-Medina, H.; Padilla-Arroyo, D.; Rivera, N.; Liriano, J.; Vega-Roman, R.; Renta, J.; Melin, K.; Duconge, J. Clinical relevant polymorphisms affecting clopidogrel pharmacokinetics and pharmacodynamics: Insights from the Puerto Rico newborn screening program. Int. J. Environ. Res. Public Health, 2018, 15(6), 1115.
[http://dx.doi.org/10.3390/ijerph15061115] [PMID: 29848980]

Flores-Gutiérrez, S.; Rodríguez-Larralde, Á.; Vívenes de Lugo, M.; Castro de Guerra, D. Distribution of polymorphisms in the CYP2C9 gene and CYP2C19/CYP2C9 haplotypes among Venezuelan populations. Ann. Hum. Biol., 2017, 44(2), 191-198.
[http://dx.doi.org/10.1080/03014460.2016.1192218] [PMID: 27230833]

de Andrés, F.; Altamirano-Tinoco, C.; Ramírez-Roa, R.; Montes-Mondragón, C.F.; Dorado, P.; Peñas-Lledó, E.M. LLerena, A. Relationships between CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 metabolic phenotypes and genotypes in a Nicaraguan Mestizo population. Pharmacogenomics J., 2021, 21(2), 140-151.
[http://dx.doi.org/10.1038/s41397-020-00190-9] [PMID: 33024249]

Isaza, C.; Henao, J.; Martínez, J.H.I.; Arias, J.C.S.; Beltrán, L. Phenotype-genotype analysis of CYP2C19 in Colombian mestizo individuals. BMC Clin. Pharmacol., 2007, 7(1), 6.
[http://dx.doi.org/10.1186/1472-6904-7-6] [PMID: 17623107]

Isaza, C.A.; Henao, J.; López, A.M.; Cacabelos, R. Isolation, sequence and genotyping of the drug metabolizer CYP2D6 gene in the Colombian population. Methods Find. Exp. Clin. Pharmacol., 2000, 22(9), 695-705.
[http://dx.doi.org/10.1358/mf.2000.22.9.802286] [PMID: 11294012]

Botton, M.R.; Campos, K.C.; Duconge, J.; Scott, S.A. Pharmacogenomics in Latin American populations. Pharmacogenomics, 2019, 329-368.
[http://dx.doi.org/10.1016/B978-0-12-812626-4.00012-7]

Roco, Á.; Quiñones, L.; Agúndez, J.A.G.; García-Martín, E.; Squicciarini, V.; Miranda, C.; Garay, J.; Farfán, N.; Saavedra, I.; Cáceres, D.; Ibarra, C.; Varela, N. Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: Comparison with Caucasian and Asian populations. Front. Genet., 2012, 3, 229.
[http://dx.doi.org/10.3389/fgene.2012.00229] [PMID: 23130019]

Varela, N.; Quiñones, L.A.; Stojanova, J.; Garay, J.; Cáceres, D.; Cespedes, S.; Sasso, J.; Miranda, C. Characterization of the CYP2D6 drug metabolizing phenotypes of the Chilean mestizo population through polymorphism analyses. Pharmacol. Res., 2015, 101, 124-129.
[http://dx.doi.org/10.1016/j.phrs.2015.07.020] [PMID: 26211952]

Vicente, J.; González-Andrade, F.; Soriano, A.; Fanlo, A.; Martínez-Jarreta, B.; Sinués, B. genetic polymorphisms of CYP2C8, CYP2C9 and CYP2C19 in ecuadorian mestizo and spaniard populations: A comparative study. Mol. Biol. Rep., 2014, 41(3), 1267-1272.
[http://dx.doi.org/10.1007/s11033-013-2971-y] [PMID: 24430292]

Machín, E. metabolic phenotypes of dextromethorphan and losartan, CYP2D6 and CYP2C9 genotypes in the ecuadorian population compared to the spanish. [Doctoral thesis]. University of Extremadura: Badajoz, 2012.

Moya, G.; Dorado, P.; Ferreiro, V.; Naranjo, M.E.G.; Peñas-Lledó, E.M. LLerena, A. High frequency of CYP2D6 ultrarapid metabolizer genotypes in an Ashkenazi Jewish population from Argentina. Pharmacogenomics J., 2017, 17(4), 378-381.
[http://dx.doi.org/10.1038/tpj.2016.27] [PMID: 27068265]

López, M.; Guerrero, J.; Jung-Cook, H.; Alonso, M.E. CYP2D6 genotype and phenotype determination in a Mexican Mestizo population. Eur. J. Clin. Pharmacol., 2005, 61(10), 749-754.
[http://dx.doi.org/10.1007/s00228-005-0038-2] [PMID: 16249913]

Carlsson, B.; Olsson, G.; Reis, M.; Wålinder, J.; Nordin, C.; Lundmark, J.; Scordo, M.G.; Dahl, M.L.; Bengtsson, F.; Ahlner, J. Enantioselective analysis of citalopram and metabolites in adolescents. Ther. Drug Monit., 2001, 23(6), 658-664.
[http://dx.doi.org/10.1097/00007691-200112000-00011] [PMID: 11802100]

Thieme, D.; Rolf, B.; Sachs, H.; Schmid, D. Correlation of inter-individual variations of amitriptyline metabolism examined in hairs with CYP2C19 and CYP2D6 polymorphisms. Int. J. Legal Med., 2008, 122(2), 149-155.
[http://dx.doi.org/10.1007/s00414-007-0184-4] [PMID: 17992535]

Aldrich, S.L.; Poweleit, E.A.; Prows, C.A.; Martin, L.J.; Strawn, J.R.; Ramsey, L.B. Influence of CYP2C19 metabolizer status on escitalopram/citalopram tolerability and response in youth with anxiety and depressive disorders. Front. Pharmacol., 2019, 10, 99.
[http://dx.doi.org/10.3389/fphar.2019.00099] [PMID: 30837874]

Gassó, P.; Rodríguez, N.; Mas, S.; Pagerols, M.; Blázquez, A.; Plana, M.T.; Torra, M.; Lázaro, L.; Lafuente, A. Effect of CYP2D6, CYP2C9 and ABCB1 genotypes on fluoxetine plasma concentrations and clinical improvement in children and adolescent patients. Pharmacogenomics J., 2014, 14(5), 457-462.
[http://dx.doi.org/10.1038/tpj.2014.12] [PMID: 24663076]

Veldic, M.; Ahmed, A.T.; Blacker, C.J.; Geske, J.R.; Biernacka, J.M.; Borreggine, K.L.; Moore, K.M.; Prieto, M.L.; Vande Voort, J.L.; Croarkin, P.E.; Hoberg, A.A.; Kung, S.; Alarcon, R.D.; Keeth, N.; Singh, B.; Bobo, W.V.; Frye, M.A. Cytochrome P450 2C19 poor metabolizer phenotype in treatment resistant depression: Treatment and diagnostic implications. Front. Pharmacol., 2019, 10, 83.
[http://dx.doi.org/10.3389/fphar.2019.00083] [PMID: 30837869]

Findling, R.L.; Nucci, G.; Piergies, A.A.; Gomeni, R.; Bartolic, E.I.; Fong, R.; Carpenter, D.J.; Leeder, J.S.; Gaedigk, A.; Danoff, T.M. Multiple dose pharmacokinetics of paroxetine in children and adolescents with major depressive disorder or obsessive-compulsive disorder. Neuropsychopharmacology, 2006, 31(6), 1274-1285.
[http://dx.doi.org/10.1038/sj.npp.1300960] [PMID: 16319918]

Chermá, M.D.; Ahlner, J.; Bengtsson, F.; Gustafsson, P.A. Antidepressant drugs in children and adolescents: analytical and demographic data in a naturalistic, clinical study. J. Clin. Psychopharmacol., 2011, 31(1), 98-102.
[http://dx.doi.org/10.1097/JCP.0b013e318205e66d] [PMID: 21192151]

Maggo, S.; Kennedy, M.A.; Barczyk, Z.A.; Miller, A.L.; Rucklidge, J.J.; Mulder, R.T.; Foulds, J.A. Common CYP2D6, CYP2C9, and CYP2C19 gene variants, health anxiety, and neuroticism are not associated with self-reported antidepressant side effects. Front. Genet., 2019, 10, 1199.
[http://dx.doi.org/10.3389/fgene.2019.01199] [PMID: 31850065]

LLerena, A.; Dorado, P.; Naranjo, M.E.G.; Peñas-Lledó, E. CYP2D6 ethnic variability in Hispanics. CYP2D6: Genetics; Pharmacology and Clinical Relevance, 2014, pp. 54-66.
[http://dx.doi.org/10.2217/fmeb2013.13.139]