PPRG Profile
UCLA Pharmacogenetics and Pharmacogenomics Research Group
| Website | http://www.depressiontreatment.org |
|---|---|
| Principal Investigator | Julio Licinio, MD |
| Host Institution | University of California, Los Angeles |
| Grant Number | U01 GM61394 |
Abstract (September, 2003 Update)
Goals
The UCLA Pharmacogenetics and Pharmacogenomics Research Group was developed to test the hypothesis that pharmacogenetic approaches can be used to optimize treatment strategies for common and complex disorders of public health relevance to Mexican-Americans, who are the poorest and most rapidly growing minority group in the U.S. To test this general hypothesis, our project has the following specific aim: To study pharmacogenetics in Mexican-Americans, using depression treatment as a proof of the concept that pharmacogenetic approaches can be used to optimize treatment strategies for common and complex disorders in this population.
This aim is addressed by a rigorous, prospective, phenotype-to-genotype study, also known as the Pharmacogenetics of Antidepressant Treatment Response In Mexican-Americans (PATRIMA) study. The phenotype component of this study consists of a clinical trial in which antidepressant treatment response is characterized in 500 patients participating is a double-blind study of desipramine or fluoxetine treatment of major depressive disorder in Mexican-Americans. For the purposes of this study, Mexican-Americans are defined as individuals with at least three grandparents born in Mexico. Treatment, treatment-response data, and DNA collection are conducted by a team of highly experienced bilingual personnel with an outstanding track record of work with the Los Angeles Mexican-American community. Phenotypic data are collected weekly over nine weeks by the same team of bilingual, experienced clinical researchers to generate a homogeneous set of continuous outcome measures.
After all samples are collected, genotyping will be done as part of a subcontract with Los Alamos National Laboratory (P.I.: John Nolan, Ph.D.), using a candidate gene strategy. Dr. Kristopher Irizarry in our group is using informatics approaches, which were strengthened by a recent bioinformatics supplement to our award, to identify SNPs in neural pathways relevant to antidepressant treatment response.
We will make the unique dataset of the phenotype and genotype of antidepressant treatment response in Mexican-Americans available to the scientific community through PharmGKB.
Progress
- Research Project:
This award has enabled us to develop a highly cohesive, bilingual research team that is focused on pharmacogenetic studies in minority populations. This project has served as a platform for professional and career development for minority scientists in our team who are working with a minority group, of which they are themselves members of. We have developed extensive liaisons with the Mexican-American community and have screened over 1,000 subjects. Of those, over 220 have enrolled in our prospective pharmacogenetic trial and 140 have completed the trial. We are now in the process of starting genotyping for an interim analysis of our existing data, while in parallel we continue to rigorously collect new clinical samples.
Our NIGMS-funded work is enriched by related projects that are funded by other sources. (1) We have developed a bioinformatics infrastructure that has permitted us to use informatics tools to identify neural candidate SNPs for psychiatric pharmacogenetic studies (submitted to publication, first author: Kristopher Irizarry). (2) We have used DNA microarrays to successfully identify in the rat molecular targets that are elicited after chronic antidepressant treatment and that are common to two different classes of antidepressant drugs (submitted to publication, first author: Ma-Li Wong). Our hypothesis is that the human orthologs of such newly identified rodent genes could become candidate targets for pharmacogenetic association studies.
In this manner, our clinical pharmacogenetic work, funded by NIGMS, informs our laboratory work because we use in the lab the same drugs that are used in the clinical pharmacogenetic work. Our laboratory work informs the clinical pharmacogenetics project, because it identifies candidate genes for genetic association. To our knowledge this is the only project of this type that is focused exclusively on an understudied minority population.
- NIGMS Repository::
We have successfully conducted two broad projects of community engagement involving the Los Angeles Mexican-American (P.I. Julio Licinio) and Han-Chinese (P.I.: Ma-Li Wong) communities that were followed by collection of 120 samples from each community, and by the creation of two ongoing Community Advisory Groups (CAG) (Mexican-American and Han-Chinese, respectively) that are related to each collection. Those two collections from Mexican-Americans and Han Chinese were deposited and are available at the Coriell Institute for Medical Research as part of the NIGMS Human Genetic Cell Repository (http://locus.umdnj.edu/nigms/). Our work has therefore already resulted in new resources for the scientific community.
- Interactions with other groups::
This network has permitted close interactions between our group and other PGRN groups that are focused on different diseases or biological systems. The result has been an exposure to various methods, ideas, and perspectives that have broadened and enriched our work. We have two manuscripts submitted to publication that are the outcome of intra-PGRN collaborations, and also have an additional ongoing line of collaboration.