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

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.

Precision Medicine in Control of Visceral Leishmaniasis Caused by L. donovani

“…In a more recent meta-analysis on the allele frequencies for 2 common liver enzymes in drug metabolism (CYP2D6 and CYP2C19), a mean risk of an abnormal CYP2D6 or CYP2C10 activity was found to be 36.4% and 61% respectively; there was major geographical variation: the range for abnormal CYP2D6 activity varied between 61% (Algeria) and 2.7% (Gambia), and for abnormal CYP2C19 between 80% (India) and 32% (Mexico) ( Koopmans et al., 2021 ). This is important in the classification of individuals as slow, normal, rapid or ultra-rapid metabolizers.…”

Pharmacogenetic Testing in an Academic Psychiatric Clinic: A Retrospective Chart Review

“…While phenotype frequencies differ among ethnicities, when comparing the phenotype frequencies of the Loyola QI population to the general world population, the Loyola cohort found an enrichment in CYP2D6 UMs with a frequency of 0.05 ( Table 2 ) [ 21 ]. Of note, the Loyola sample refers to *1/*17 as NM, whereas the Clinical Pharmacogenetics Implementation Consortium (CPIC) and PharmVar reference refers to *1/*17 as UM.…”

Population pharmacogenomics: an update on ethnogeographic differences and opportunities for precision public health

“…Considerable numbers of CYP2C19 PMs were also reported in East Asian (14.2%) and Central/South Asian (11.8%) populations, whereas their numbers are lower in Latin America (1.1%), Europe (2.7%) and Africa (3.3%). CYP2C19 UMs are most common in European, African and Latin American populations with frequencies pivoting around 20-30%, whereas only 2.1% of the East Asians are UMs (Koopmans et al 2021 1 and 2; Supplementary Table 1). Countries are color-coded with the highest frequency in red, the average frequency across all populations ( f ) in yellow, and the lowest frequency in green.…”