Interindividual variation in response to drug administration is multi-factorial, with genetic factors often contributing significantly. Because of the difficulfies in studying drug response in humans, cell-based models are being developed as a means to identify and characterize genetic markers associated with drug response. Particulariy with the availability of extensive genotypic (e.g. SNPs and copy number variants) and phenotypic (e.g., gene expression) data for the International HapMap cell lines, investigators have begun to analyze pharmacological endpoints within these lines in efforts to identify clinically important genotype-phenotype relafionships. Over the past 5 years, there has been significant growth in the number of PGRN investigators employing cell-based models as a component of their pharmacogenomic research program (Figure 1). Some PGRN groups (PAAR, CREATE, PPII) have utilized the International HapMap and or the Polymorphism Discovery lymphoblastoid cell lines (LCLs) that are commercially available from the Coriell Institute for Medical Research (www.coriell.org/). Other groups have created their own cell lines from individuals with a specific disease such as asthma (PHAT) or hypertension (PEAR), or they have generated cell lines from key individuals in deeply-phenotyped populafions such as the Amish (PAPI) or SOPHIE (healthy volunteers) study (PMT). Therefore, providing a resource for the exchange of information generated via the use of cell lines would be highly beneficial to the majority of existing PGRN groups (8 out of 11). This resource will also be of great benefit to PGRN invesfigators who currently do not use cell-based models, because it will provide them with opportunities to learn about the applications for cell-based research and invesfigate results of pharmacogenomic studies within this model system.
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