CYP2D6 -1584C>G Promoter Polymorphism and Debrisoquine Ultrarapid Hydroxylation in Healthy Volunteers

Abstract

The CYP2D6 -1584C>G polymorphism (rs1080985) has been identified as a major factor for CYP2D6 expression and function, with the mutant -1584G promoter type being consistently associated with significantly greater expression than -1584C. It may therefore be associated with ultrarapid metabolism. The objective of the present study was to explore the relationship between the CYP2D6 -1584C>G polymorphism and the debrisoquine metabolic ratio in healthy volunteers in order to evaluate its potential impact on the ultrarapid CYP2D6 hydroxylation capacity. The CYP2D6 -1584C>G polymorphism was analyzed in 320 unrelated healthy individuals who were previously phenotyped for debrisoquine hydroxylation. The metabolic ratio (log10 mean ± standard deviation) of individuals with the -1584G allele was lower than that of individuals with the -1584C allele for carriers of one active CYP2D6 gene (-0.13 ± 0.33 and 0.17 ± 0.52, respectively; p < 0.05) or two active CYP2D6 genes (-0.32 ± 0.39 and -0.20 ± 0.44, respectively; p < 0.05). The presence of the -1584G allele in the promoter region of the CYP2D6 gene was related to a high CYP2D6 hydroxylation capacity.