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Pharmacogenomics. 2013 Dec;14(16):1973-7. doi: 10.2217/pgs.13.181.

CYP2D6 -1584C>G promoter polymorphism and debrisoquine ultrarapid hydroxylation in healthy volunteers.

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1
CICAB Clinical Research Centre, Extremadura University Hospital & Medical School, Badajoz 06080, Spain.

Abstract

BACKGROUND & AIM:

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.

MATERIALS & METHODS:

The CYP2D6 -1584C>G polymorphism was analyzed in 320 unrelated healthy individuals who were previously phenotyped for debrisoquine hydroxylation.

RESULTS:

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).

CONCLUSION:

The presence of the -1584G allele in the promoter region of the CYP2D6 gene was related to a high CYP2D6 hydroxylation capacity.

PMID:
24279852
DOI:
10.2217/pgs.13.181
[Indexed for MEDLINE]
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