CYP2C:TG haplotype in Ecuador and Nicaragua: insights into CYP2C19 genotype–phenotype correlation in context to Mestizo populations

Résumé fourni par la source

The impact of the CYP2C:TG haplotype on CYP2C19-mediated omeprazole metabolism was evaluated. CYP2C19 enzymatic activity was assessed in 234 volunteers from Nicaragua and Ecuador using the omeprazole/5-hydroxyomeprazole metabolic ratio within a validated CEIBA cocktail protocol. Genotyping included CYP2C19 alleles (*2, *3, *4, *5, *17) and CYP2C:TG defining CYP2C18 variants (rs2860840, rs11188059). Associations among the CYP2C:TG haplotype, CYP2C19 genotype, and metabolic ratio were analyzed using univariate and multivariate models. The CYP2C:TG haplotype was the second most frequent (33.76%) and occurred exclusively with the CYP2C19 *1 allele. No significant association was observed between CYP2C:TG haplotype and the metabolic ratio (p = 0.12). Across predicted metabolizer groups, a trend toward increased CYP2C19 metabolism was observed, although this difference did not reach statistical significance. In these admixed Latin American populations, the CYP2C:TG haplotype was not significantly associated with CYP2C19-mediated omeprazole metabolism. This finding does not support clinical implementation of CYP2C:TG haplotype testing for predicting CYP2C19 activity and underscores the need for further research on this haplotype and its potential role in CYP2C19 metabolism across diverse populations in the context of pharmacogenetics.

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