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2. CYP2D6 Pharmacogenomics: From Genotype to Phenotype
Simon Kung, M.D.
Associate Professor of Psychiatry
Mayo Clinic

3. CYP2D6 Common Alleles Allele Frequency (Caucasians) Allele
Functional Status
Activity Level *1
Normal 1
39% *2
Normal 1
28% *3
None
1.3% *4
None
18% *5
None
2.8% *9
Decreased
0.5
2.1%
*10
Decreased
0.5
2.9%
*41
Decreased
0.5
7.7%
Duplications
Increased
>1
2.7%
Hicks, J. K., Sangkuhl, K., Swen, J. J., Ellingrod, V. L., Müller, D. J., Shimoda, K., ... & Dunnenberger, H. M. (2017). Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clinical Pharmacology & Therapeutics, 102(1),

4. Africans and Middle Easterners:
Allele Frequency and Geography
Allele Frequency
(Caucasians)
Allele
Functional Status
East Asians:
Allele frequency is 0.5%. *1
Normal
39% *2
Normal
28% *3
None
1.3% *4
None
18% *5
None
2.8%
Africans and Middle Easterners:
Allele frequency
is 7%. *9
Decreased
2.1%
*10
Decreased
2.9%
*41
Decreased
7.7%
Duplications
Increased
2.7%
Hicks, J. K., Sangkuhl, K., Swen, J. J., Ellingrod, V. L., Müller, D. J., Shimoda, K., ... & Dunnenberger, H. M. (2017). Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clinical Pharmacology & Therapeutics, 102(1),

5. Metabolizer Phenotype
Mapping Genotype to Phenotype
Metabolizer Phenotype
Genotype
*4/*4
Poor
Intermediate
*1/*4
Normal (extensive)
*1/*1
Ultrarapid
Duplications
Hicks, J. K., Sangkuhl, K., Swen, J. J., Ellingrod, V. L., Müller, D. J., Shimoda, K., ... & Dunnenberger, H. M. (2017). Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clinical Pharmacology & Therapeutics, 102(1),

6. CYP2D6 Relative Percentages
Metabolizer
Percentages
5-10%
Poor
Intermediate
2-11%
Normal (extensive)
77-92%
Ultrarapid
1-7%
Hicks, J. K., Sangkuhl, K., Swen, J. J., Ellingrod, V. L., Müller, D. J., Shimoda, K., ... & Dunnenberger, H. M. (2017). Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clinical Pharmacology & Therapeutics, 102(1),
Porcelli, S., Drago, A., Fabbri, C., Gibiino, S., Calati, R., & Serretti, A. (2011). Pharmacogenetics of antidepressant response. Journal of psychiatry & neuroscience: JPN, 36(2), 87.

7. Key Points
P450 2D6 is highly polymorphic, and it does vary across geography.
About 10% of Caucasians are poor metabolizers, and up to 7% are ultrarapid metabolizers.
In Africa and the Middle East, there is a higher prevalence of ultrarapid metabolizers.

8. Next Presentation CYP2C19 Pharmacogenomics: Alleles, Variation, and Phenotype