Identification of genetic variants and gene expression relationships associated with pharmacogenes in humans.
OBJECTIVE
The very important pharmacogenes (VIPs) were selected by Pharmacogenetic Research Network (National Institutes of Health-PGRN) owing to their significant effects on drug treatment both at the pharmacokinetic and pharmacodynamic levels. Our objective was to identify single nucleotide polymorphisms (SNPs) that potentially affected the expression of these genes or potential SNP-gene interactions involved to improve our understanding of genetic effects on drug therapy.


METHODS
Gene expression was evaluated in 176 International HapMap lymphoblastoid cell lines derived from CEU (CEPH, Utah residents with ancestry from northern and western Europe; n=87) and YRI (Yoruba in Ibadan, Nigeria; n=89) using Affymetrix GeneChip Human Exon 1.0 ST arrays (Affymetrix Laboratory, Affymetrix Inc., Santa Clara, California, USA) with interrogation of greater than 17,000 human genes. Genome-wide association was performed between over two million publicly available HapMap SNPs and gene expression.


RESULTS
The expression of two PGRN-VIPs (GSTT1 and GSTM1) are significantly associated with SNPs within 2.5 Mb of the genes; whereas the expression of three and ten PGRN-VIPs are significantly associated with distant-acting SNPs in CEU and YRI, respectively. In addition, three and four PGRN-VIPs harbor SNPs that are distantly associated with other gene expressions in CEU and YRI, respectively.


CONCLUSIONS
Using this information, one may identify genetic variants that are significantly associated with the expression of any set of genes of interest; or evaluate potential gene-gene interaction through SNP expression relationships.
Huang
Rong Stephanie
RS
Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Duan
Shiwei
S
Kistner
Emily O
EO
Zhang
Wei
W
Bleibel
Wasim K
WK
Cox
Nancy J
NJ
Dolan
M Eileen
ME
D044383:Black People / Q000235:genetics; D002460:Cell Line; D015870:Gene Expression; D014644:Genetic Variation; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
D005982:Glutathione Transferase; C413545:glutathione S-transferase T1