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Identification of CYP2D6 impaired functional alleles in Mexican Americans

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objectives

To extend the genotyping analysis of the CYP2D6 gene and further explain variability of CYP2D6 activity in Mexican Americans by genetic factors.

Methods

CYP2D6 gene sequence variations associated with *6, *7, *8, *9, *11, *14, *29, *41, *45, and *46 alleles as well as the 2988G>A SNP were examined in 264 Mexican Americans; 236 had previously been phenotyped with dextromethorphan. All subjects were previously genotyped for CYP2D6*2, *3, *4, *5, *10, *17, and the presence of a gene duplication. Associations between genotype and CYP2D6 activity were determined.

Results

Mexican Americans revealed a high frequency of functional alleles (CYP2D6*1 and *2; 73.1%), followed by CYP2D6*4 (non-functional, 10.0%) and the reduced-function allele *41 (9.5%). The frequencies of CYP2D6*5, *6, *9, *10, duplication, and 2988A were 1.7%, 0.4%, 1.1%, 2.8%, 0.8%, and 5.7%, respectively. CYP2D6*3, *17, and *29 were found only in one individual (CYP2D6*2/*3, *1/*17, and *4/*29), while CYP2D6*7, *8, *11, *14, *45, and *46 were absent in this study population. Decreased CYP2D6 activity was more accurately predicted by the presence *41[−1584C] compared to *41[2988A]. One genotype/phenotype discordant subject was resolved by the presence of a CYP2D6*6 allele (*4/*6), while two other cases remained discordant (*41/*41 and *1/*1).

Conclusions

The CYP2D6*4, *5, and *6 null alleles along the reduced function alleles *9, *10, and *41 are the major cause for diminished dextromethorphan oxidative capacity in Mexican Americans. These findings may have implications for the safety and efficacy of CYP2D6 substrates taken by Mexican Americans.

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Acknowledgements

This study is supported by NIH/NIAAA grant AA012081.

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Authors and Affiliations

  1. Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Mail Stop 1018 Breidenthal Building 3901 Rainbow Blvd, 66160-7417, Kansas, KS, USA

    Huai-Rong Luo, Vasileios Aloumanis & Yu-Jui Yvonne Wan

  2. Division of Pediatric Clinical Pharmacology and Medical is extremely polymorphic, Toxicology, Children's Mercy Hospital and Clinics, Kansas, MO, USA

    Andrea Gaedigk

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  1. Huai-Rong Luo
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  2. Andrea Gaedigk
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Correspondence to Yu-Jui Yvonne Wan.

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Luo, HR., Gaedigk, A., Aloumanis, V. et al. Identification of CYP2D6 impaired functional alleles in Mexican Americans. Eur J Clin Pharmacol 61, 797–802 (2005). https://doi.org/10.1007/s00228-005-0044-4

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  • DOI: https://doi.org/10.1007/s00228-005-0044-4

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