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Review
. 2021 Feb 24;11(1):141.
doi: 10.1038/s41398-020-01129-1.

Meta-analysis of probability estimates of worldwide variation of CYP2D6 and CYP2C19

Anne B Koopmans  1   2 , Mario H Braakman  3   4 , David J Vinkers  5 , Hans W Hoek  6   7   8 , Peter N van Harten  5   9
Affiliations
Review

Meta-analysis of probability estimates of worldwide variation of CYP2D6 and CYP2C19

Anne B Koopmans et al. Transl Psychiatry. .

Abstract

Extensive migration has led to the necessity of knowledge regarding the treatment of migrants with different ethnical backgrounds. This is especially relevant for pharmacological treatment, because of the significant variation between migrant groups in their capacity to metabolize drugs. For psychiatric medications, CYP2D6 and CYP2C19 enzymes are clinically relevant. The aim of this meta-analysis was to analyze studies reporting clinically useful information regarding CYP2D6 and CYP2C19 genotype frequencies, across populations and ethnic groups worldwide. To that end, we conducted a comprehensive meta-analysis using Embase, PubMed, Web of Science, and PsycINFO (>336,000 subjects, 318 reports). A non-normal metabolizer (non-NM) probability estimate was introduced as the equivalent of the sum-prevalence of predicted poor, intermediate, and ultrarapid metabolizer CYP2D6 and CYP2C19 phenotypes. The probability of having a CYP2D6 non-NM predicted phenotype was highest in Algeria (61%) and lowest in Gambia (2.7%) while the probability for CYP2C19 was highest in India (80%) and lowest in countries in the Americas, particularly Mexico (32%). The mean total probability estimates of having a non-NM predicted phenotype worldwide were 36.4% and 61.9% for CYP2D6 and CYP2C19, respectively. We provide detailed tables and world maps summarizing clinically relevant data regarding the prevalence of CYP2D6 and CYP2C19 predicted phenotypes and demonstrating large inter-ethnic differences. Based on the documented probability estimates, pre-emptive pharmacogenetic testing is encouraged for every patient who will undergo therapy with a drug(s) that is metabolized by CYP2D6 and/or CYP2C19 pathways and should be considered in case of treatment resistance or serious side effects.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. PRISMA flow diagram of the studies included in the analyses.
n = number of studies.
Fig. 2
Fig. 2. CYP2D6 non-normal probability estimate per country.
Country (genotyped subjects); non-normal probability estimate in percentage.
Fig. 3
Fig. 3
Worldwide CYP2D6 non-normal metabolizer probability estimates.
Fig. 4
Fig. 4. CYP2C19 non-normal probability estimates per country.
Country (genotyped subjects); non-normal probability estimate in percentage.
Fig. 5
Fig. 5
Worldwide CYP2C19 non-normal metabolizer probability estimates.
See this image and copyright information in PMC

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