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Interethnic differences in UGT1A4 genetic polymorphisms between Mexican Mestizo and Spanish populations

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Abstract

UDP-glucuronosyltransferase 1A4 (UGT1A4) is a phase II drug-metabolizing enzyme that catalyzes the glucuronidation of many clinically-important drugs. Interethnic differences in the genetic polymorphism of UGT1A4 have been reported; however, there is no information in Mexican Mestizos (MMs) and Spaniards (SPs). Furthermore, MM is an admixed population with 26 % of Caucasian genes mainly from Spain. Therefore, this study aimed to investigate the potential differences between 318 SPs and 248 MMs healthy individuals regarding UGT1A4*1b, UGT1A4*2 and UGT1A4*3 alleles and to compare the observed frequencies with those previously reported in different populations. The allelic frequencies of the three UGT1A4 polymorphisms showed interethnic differences between MMs and SPs (p < 0.05). The analyzed SNPs variants in this genetic region were not in linkage disequilibrium (LD) for the MM population, suggesting that these mutations have arisen independently in the same genetic background. In contrast, UGT1A4*2 and UGT1A4*3 were in LD in the SP population. Comparison of present data with other in different ethnic groups revealed that the frequencies of UGT1A4*2 and UGT1A4*3 in SP were similar to other Caucasians and higher than in Asians, whereas in MMs were lower than in Caucasians and higher than in Asians only for UGT1A4*2. Present results could be helpful to improve the use of UGT1A4 drug substrates in order to adjust them to the ethnic background of a given population, specifically for Hispanics.

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Acknowledgments

The study has been partly supported by the Institute of Health Carlos III-FIS and the European Union (FEDER) Grants PI10/02758, PI10/02010 and CP06/00030 (P. Dorado) and from PRIS Extremadura, Consejería de Sanidad y Dependencia, FundeSalud PRIS10043 and PRIS11051 Gobierno de Extremadura AEXCID Cooperacion Extremeña (11IA002); by a Grant from Consejo Nacional de Ciencia y Tecnología de Mexico (CONACYT #167261) and was coordinated in the SIFF-RIBEF network (Red Iberoamericana de Farmacogenética y Farmacogenomica; www.ribef.com). The technical assistance of Esther Machín, Inés López and Beatriz Grillo is gratefully acknowledged.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Biological Systems, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico

    Marisol López & Alberto Ortega

  2. CICAB Centro de Investigación Clínica CIBERSAM, SES Servicio Extremeño de Salud, Hospital Universitario Infanta Cristina, 06080, Badajoz, Spain

    Pedro Dorado, Eva Peñas-Lledó, Jesús Cobaleda, Alicia Gallego-Aguilera & Adrián LLerena

  3. Department of Neurogenetics and Molecular Biology, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico

    Nancy Monroy & María Elisa Alonso

  4. Department of BioAnalytical Sciences, Nestlé Research Center, Vers-chez-les-Blanc, Lausanne, Switzerland

    Irma Silva-Zolezzi

  5. Centro de Salud Ciudad Jardín, SES Servicio Extremeño de Salud, Badajoz, Spain

    Jesús Cobaleda

Authors
  1. Marisol López
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  2. Pedro Dorado
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  3. Alberto Ortega
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  4. Eva Peñas-Lledó
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  5. Nancy Monroy
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  6. Irma Silva-Zolezzi
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  7. Jesús Cobaleda
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  8. Alicia Gallego-Aguilera
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  9. María Elisa Alonso
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  10. Adrián LLerena
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Corresponding author

Correspondence to Adrián LLerena.

Additional information

Marisol López and Pedro Dorado contributed equally to this work.

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López, M., Dorado, P., Ortega, A. et al. Interethnic differences in UGT1A4 genetic polymorphisms between Mexican Mestizo and Spanish populations. Mol Biol Rep 40, 3187–3192 (2013). https://doi.org/10.1007/s11033-012-2393-2

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  • DOI: https://doi.org/10.1007/s11033-012-2393-2

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