title: 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.
authors: 1] CICAB Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain [2] CIBERSAM, Instituto de Salud Carlos III, Madrid, Spain.
authors: A
authors: A
authors: Llerena
authors: Faculty of Medical Sciences and Faculty of Medicine 'Calixto García', Havana, Cuba.
authors: M
authors: M
authors: Alvarez
authors: CICAB Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain.
authors: P
authors: P
authors: Dorado
authors: Faculty of Medical Sciences and Faculty of Medicine 'Calixto García', Havana, Cuba.
authors: I
authors: I
authors: González
authors: CICAB Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain.
authors: E
authors: E
authors: Peñas-LLedó
authors: Faculty of Medical Sciences and Faculty of Medicine 'Calixto García', Havana, Cuba.
authors: B
authors: B
authors: Pérez
authors: 1] CICAB Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain [2] Centro de Salud Ciudad Jardín SES, Badajoz, Spain.
authors: J
authors: J
authors: Cobaleda
authors: Centro Comunitario de Salud Mental La Habana Vieja, La Habana, Cuba.
authors: L R
authors: LR
authors: Calzadilla
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D003462:Cuba / Q000208:ethnology; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D004008:Diclofenac / Q000378:metabolism*; D005006:Ethnicity / Q000235:genetics*; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D013030:Spain / Q000208:ethnology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D065729:Cytochrome P-450 CYP2C9