Netherlands, the

CYP2C19 (measured phenotype):
Dutch Caucasians
98.2 % extensive metabolizers
1.8 % poor metabolizers
(N=4301, Dutch healthy volunteers, 98.9% Caucasian, 68% males)(Tamminga et al., 1999).
[Note editor: Study-population is allocated to two categories: extensive or poor metabolizers; superextensive and slow metabolizers are not mentioned. Apparently extensive and superextensive are lumped together into ‘extensive metabolizers’ and slow and poor metabolizers into ‘poor metabolizers’]

CYP 2C19

CYP 2C19 substrates

amitriptyline

citalopram

clomipramine

diazepam

imipramine

Source: Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine

(2007). "http://medicine.iupui.edu/clinpharm/ddis/clinical-table/".

CYP 2C19 basic facts:

Cytochrome P450 2C19 (or CYP2C19) is a drug-metabolizing enzyme involved in the first phase metabolism of many drugs. CYP2C19 protein is encoded by the CYP2C19 gene.The CYP2C19 gene is polymorphic, at this moment more than 45 allelic variants have been described (an overview can be found at http://www.cypalleles.ki.se/cyp2c19.htm).

CYP2C19*1 is the normal variant, a functional allele, also called the wild-type (wt). CYP2C19*2 and CYP2C19*3 are inactive alleles and have a predicted poor metabolism CYP2C19*17 is the increased activity allele, which means that individuals with that is wt/*17 or *17/*17 genotypes, are considered as ultrarapid metabolizers (Fricke-Galindo et al.2015).

Fricke-Galindo et al. 2015 calculated the correlation between the frequencies of CYP2C19 genetically expected PMs and the phenotypically measured PMs and found a very high correlation by ethnic group (r = 0.94, p < 0.001) and an even higher correlation by geographic region (r=0.99, p = 0.002). This indicates a very close relationship between genotype and phenotype.

Interethnic variability around the world:

Fricke-Galindo et al. studied the worldwide frequency distribution of CYP2C19 alleles (genetically predicted metabolic functioning) and actually measured CYP2C19 metabolic phenotypes among healthy volunteers from different ethnic groups and geographic regions.

Their findings:

Ethnicity:

CYP2C19*17 was 42-fold more frequent in Mediterranean-South Europeans than in East Asians.
CYP2C19*17 was 24-fold more frequent in Middle Easterns than in East Asians.
In East Asians CYP2C19*2 (30,26%) and CYP2C19*3 (6,89%) alleles were more frequent.
In native populations from Oceania CYP2C19*2 was found in 61.30% of the subjects and in 14.42% CYP2C19*3 was found.

Geography:

Actually measured PMs were found in lowest frequency in populations from Europe (2.24%). Actually measured PMs were found in a high frequency in Asia (14.56%).
These findings are derived from a high quality systematic review by Fricke-Galindo et al.2015. Their analysis included 52181 healthy volunteers within 138 selected original research papers.

5Protein CYP2C19 PDB 1r9o

^{By Emw - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8766981 retrieved March 14th, 2016}

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