Pharmacogenomics (Epub ahead of print) ISSN 1462-2416
part of
Pharmacogenomics
Research Article
10.2217/PGS.15.24 © Future Medicine Ltd
Aim: To analyze the distribution of CYP2D6 variants in two ethnically-related
Mexican Native and Mestizo populations cohabitating the same econiche and their
relationships with a distant Mestizo community. Materials & methods: 314 volunteers
were genotyped for CYP2D6 gene variants (*2, *3, *4, *6, *10, *13, *17 , *35 and *41)
using predesigned TaqMan probes. CYP2D6*5 and CYP2D6 wtxN were assessed by
XL-PCR. Results: CYP2D6*1, *2, *4 and *10 variants represented above 80.9% of total
alleles. Chiapanecan communities showed low allele diversity compared with the
northeastern population. Principal component analyses demonstrated clustering of
both Mestizo populations. Variants associated to ultrarapid and poor metabolism
were rare in Natives. Conclusion: Sharing of CYP2D6 alleles in both Chiapanecan
populations suggests an ongoing gene-flow.
Original submitted 8 December 2014; Revision submitted 13 February 2015
Keywords: CYP2D6•Mestizo•NativeAmerican•PCAanalysis•population
pharmacogenetics
Cytochrome P450 enzymes play an impor-
tant role in xenobiotics metabolism [1] . A key
member of this group is the CYP2D6 enzyme
(gene locus: 22q13.2), involved in the bio-
transformation of about 20–25% of the
exogenous and endogenous cell compounds,
including some antidepressants, antipsychot-
ics, antiarrhythmics, opiate analgesics, anti-
emetics and β-blockers. Such drugs have a
narrow therapeutic window that could be
modified by factors as age, enzyme induction
or inhibition, co-treatments and gene poly-
morphisms, including whole gene deletions
and duplications resulting in enzymes with
increased, poor or null activity [2] . More than
50 CYP2D6 allelic variants are reported that
determine a huge range of enzyme activity [3] .
CYP2D6 alleles impacting the functional
phenotype are those involved in protein con-
formational changes and gene copy-number
variants, including CYP2D6*3, CYP2D6*4,
CYP2D6*4M, CYP2D6*5 and CYP2D6*6
alleles conferring null to low activity;
CYP2D6*10, CYP2D6*17 and CYP2D6*41
associated to reduced activity; CYP2D6*1
and CYP2D6*2 related to normal activity
and gene duplications (wtxN) associated to
increased activity. These alleles are useful for
functional phenotypic predictions in about
90% of Caucasian subjects [4] . CYP2D6
genotypes may predict four functional
groups with predicted genotypes ultrarapid
(UM) with more than three functional gene
copies, extensive (EM) with at least one func-
tional allele, intermediate in subjects carry-
ing an allele with reduced or null activity and
poor metabolizers (PM) in subjects carrying
two reduced or inactive alleles. It has been
demonstrated that these functional pheno-
types could be correlated to pharmacological
poor outcomes and adverse events.
The wide spectrum of CYP2D6 gene
variations also allows for the opportunity to
develop population studies, which may be
useful to predict pharmacological outputs in
a defined community. Mestizos and Native
Interethnic relationships of CYP2D6
variants in native and Mestizo populations
sharing the same ecosystem
Yadira Xitlalli
Perez-Paramo
1
, Francisco
Hernandez-Cabrera
2
, Pedro
Dorado
3,4
, Adrian Llerena
3
,
Sergio Muñoz-Jimenez
5
,
Rocio Ortiz-Lopez
1
& Augusto Rojas-Martinez*
,1
1
DepartamentodeBioquímicayMedicina
Molecular,FacultaddeMedicina&
CentrodeInvestigaciónyDesarrollo
enCienciasdelaSalud,Universidad
AutónomadeNuevoLeón,Carlos
CansecoS.N.,ColoniaMitrasCentro,
Monterrey,C.P.64460,Mexico
2
CentrodeInvestigaciónenMatemáticas,
Monterrey,Mexico
3
CICAB,ClinicalResearchCentre
ExtremaduraUniversityHospital&
MedicalSchool,Badajoz06080,Spain
4
UniversityofExtremadura,Plasencia,
Spain
5
ClínicaEsquipulas,SanCristóbaldelas
Casas,Mexico
*Authorforcorrespondence:
Tel.:+528113404370
Fax:+528183337747
arojasmtz@gmail.com
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