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Interethnic differences in the relevance of CYP2C9 genotype and environmental factors for diclofenac metabolism in Hispanics from Cuba and Spain

Abstract

The aims of this study were to evaluate the diclofenac metabolism in Hispanics from Cuba and Spain and its relation to ethnicity, CYP2C9 genotypes and environmental factors. Diclofenac hydroxylation capacity (concentration ratios of diclofenac/metabolites in 8-h urine) was studied in 160 Cuban (classified as 76 Cuban-Whites—CWs and 84 Cuban-Mestizos—CMs) and 148 Spaniard (SPs) healthy volunteers. Diclofenac and its main metabolites, 4′-hydroxy (OH), 3′-OH and 5-OH diclofenac, and CYP2C9*2 to *6 and *8 alleles were also determined in 132 and 128 CWs and CMs, respectively. Gender, tobacco, caffeine and ethanol consumption were also evaluated. The mean diclofenac/4′-OH diclofenac ratio was higher in CMs (0.72±0.25) than in CWs (0.64±0.20; P<0.05) and SPs (0.57±0.26; P<0.001). The mean diclofenac/4′-OH diclofenac ratio was higher (P<0.05) in subjects with CYP2C9*1/*3 (0.77±0.19; n=22) and CYP2C9*1/*8 (0.93±0.33; n=4) genotypes than with CYP2C9*1/*1 (0.65±0.24; n=90). Environmental factors did not seem to influence the diclofenac metabolism in these populations. The present findings show for the first time interethnic differences between Hispanic groups in urinary diclofenac/4′-OH diclofenac ratios, and the relevance of CYP2C9*3 and CYP2C9*8 alleles.

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Acknowledgements

The study has been partly supported by the Institute of Health Carlos III-FIS and the European Union (FEDER) Grants PI10/02010 and PI10/02758, and by the Gobierno de Extremadura and FEDER Grants PRIS11051 and BS10023. This work also received a proportion of funding from AEXCID Cooperación Extremeña of the Junta de Extremadura (11IA002) to SIFF Sociedad Iberoamericana de Farmacogenetica, and it was coordinated in the RIBEF network (Red Iberoamericana de Farmacogenética y Farmacogenómica; www.ribef.com).

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Llerena, A., Alvarez, M., Dorado, P. et al. Interethnic differences in the relevance of CYP2C9 genotype and environmental factors for diclofenac metabolism in Hispanics from Cuba and Spain. Pharmacogenomics J 14, 229–234 (2014). https://doi.org/10.1038/tpj.2013.28

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Keywords

  • CYP2C9
  • diclofenac
  • genotype
  • phenotype
  • environmental factors
  • Hispanics

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