1] CICAB Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain [2] CIBERSAM, Instituto de Salud Carlos III, Madrid, Spain.
Faculty of Medical Sciences and Faculty of Medicine 'Calixto García', Havana, Cuba.
Pharmacogenomics J. 2014 Jun;14(3):229-34. doi: 10.1038/tpj.2013.28. Epub 2013 Aug 20.
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 CYP2C91/3 (0.77±0.19; n=22) and CYP2C91/8 (0.93±0.33; n=4) genotypes than with CYP2C91/1 (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 CYP2C93 and CYP2C98 alleles.
本研究旨在评估西班牙裔古巴人和西班牙人（分别归类为 76 名古巴白人-CWs 和 84 名古巴混血儿-CMs）的双氯芬酸代谢及其与种族、CYP2C9 基因型和环境因素的关系。研究人员检测了 160 名古巴（76 名古巴白人-CWs 和 84 名古巴混血儿-CMs）和 148 名西班牙志愿者（SPs）的双氯芬酸羟化能力（8 小时尿液中双氯芬酸/代谢物的浓度比）。此外，研究人员还在 132 名和 128 名 CWs 和 CMs 中分别检测了双氯芬酸及其主要代谢物 4'-羟基（OH）、3'-OH 和 5-OH 双氯芬酸，以及 CYP2C9*2 到 6 和 8 等位基因。研究人员还评估了性别、吸烟、咖啡因和乙醇的摄入量。CMs（0.72±0.25）的双氯芬酸/4'-OH 双氯芬酸比值高于 CWs（0.64±0.20；P<0.05）和 SPs（0.57±0.26；P<0.001）。CYP2C91/3（0.77±0.19；n=22）和 CYP2C91/8（0.93±0.33；n=4）基因型的双氯芬酸/4'-OH 双氯芬酸比值高于 CYP2C91/1（0.65±0.24；n=90）（P<0.05）。环境因素似乎并没有影响这些人群中双氯芬酸的代谢。本研究首次发现，西班牙裔人群中，不同种族之间的尿液双氯芬酸/4'-OH 双氯芬酸比值存在差异，且 CYP2C93 和 CYP2C98 等位基因具有相关性。
