High Througput Analysis of Genetic Diverstiy in ADME Related Genes

21 Pages·2010·4.2 MB·English

by  David Valle

www.inmegen.gob.mx
High Througput Analysis of Genetic Diverstiy in
ADME Related Genes in the Mexican Population:
PGENI Mexico
1st Latin American Pharmacogenomics and Personalized Medicine
Congress
Dr. Alfredo Hidalgo Miranda
INMEGEN, Mexico
May 13, 2010, San Juan, Puerto Rico
Clinical Trials, Pharmacogenomics and
Genomic Diversity
 Generalization in Clinical Trials is just not possible
 In the short-term future, clinical trials will have to include genomic information of
different populations to get a better evaluation of the drug’s efficacy and safety
 Clinical randomized trials are increasingly being done outside the US
 Publicly available population datasets, like the HapMap, do not fully represent
genomic diversity of the original populations
 Unfortunately, not every country has the necessary infrastructure, human and
economical resources to perform genomic analyses
 Given the above, a good starting point is to describe the general genomic diversity
in ADME related genes in different and diverse populations worldwide
Mexican Mestizos Have a Source of Genetic
Diversity not Represented in the HapMap
CEU
Mestizos
YRI
ZAP
JHC
Silva-Zolezzi I, Proc Natl Acad Sci U S A. 2009 May 26;106(21):8611-6.
Genotyping and Gene Expression Core Unit:
Affymetrix and Illumina
Supercomputing and Computational Genomics
Genes & markers in the DMET Plus Panel
1,936 functional mutations in 225 genes
Markers in all FDA-validated genes
DPYD
CYP2D6 50
45
NAT1
CYP2C9 CYP450
Phase II
NAT2
CYP1A1
enzymes
enzymes
GSTT1
CYP1B1
UGT1A1
CYP2C19
478 408
UGT1A9
CYP4F2
66
MDR1 PPARD
64
Transcription
ABCC1 PPARG
Drug
regulators &
ABCG2 AHR
transporters
other enzymes
SLCO1A2 ARNT
SULT1A1 RXRA
637 413
SULT4A1 NR1I2
© PGENI-INMEGEN 2010
Molecular Inversion Probes
© PGENI-INMEGEN 2010
PharmacoGenomics for Every Nation
Initiative DMET Map: Starting a Global PG
map
 Initial Phase of PGENI’s Worldwide DMET Map
 Genotyping of more than 700 individuals from around the world
 7 designed regional centers in 4 continents
 20 different human populations
© PGENI-INMEGEN 2010
PGENI DMET Map: Starting a Global PG map
Jordan
1 population
China
2 populations
Ghana
2 populations
Mexico
2 populations
India
2 populations
Brazil
3 populations
South-Africa
5 populations
© PGENI-INMEGEN 2010