The focus of the proposed UCLA Pharmacogenetics and Pharmacogenomics Research Group (PPRG) is the pharmacogenetics and pharmacogenomics of depression in Mexican-Americans. Depression is a common, complex disorder of unknown cause that affects 15 percent of the population, costing over 40 billion dollars to the U.S. economy annually. The pharmacogenetics of depression is therefore of great relevance to public health. The UCLA PPRG will study the clinical pharmacogenetics of antidepressant treatment response in Mexican-Americans.
This specific aim will be addressed by a complementary project. Project 1 (specific aim 1) examines phenotype-genotype interactions in 800 Mexican-Americans subjects suffering from major depression. This will be a double-blind, randomized 8-week trial of two antidepressant drugs, one predominantly serotoninergic and the other predominantly norepinephrinergic; 400 patients will be assigned randomly to each drug. We will verify whether polymorphisms of relevant candidate genes are associated with treatment response. Clinical data and DNA obtained in this study will be deposited in the proposed UCLA PPRG DNA Bank, to become a national resource that will be available to other research groups. This project will be developed at UCLA by a cohesive, cross-disciplinary group of expert investigators that can utilize the data generated within the UCLA PPRG to inform and enrich the project. This ability to go from molecule to man, using the tools of contemporary biology to generate a coherent and synergist body of work that integrates pharmacogenetic and pharmacogenomic research at the genetic, molecular, cellular, integrative, behavioral, clinical levels is a key feature of the UCLA PPRG. Our data will be deposited in the NIGMS pharmacogenetics database.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01GM061394-01S1
Application #
6414352
Study Section
Special Emphasis Panel (ZRG1 (01))
Program Officer
Long, Rochelle M
Project Start
2000-04-01
Project End
2001-07-31
Budget Start
2000-04-01
Budget End
2001-07-31
Support Year
1
Fiscal Year
2001
Total Cost
$156,068
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Yu, C; Arcos-Burgos, M; Licinio, J et al. (2017) A latent genetic subtype of major depression identified by whole-exome genotyping data in a Mexican-American cohort. Transl Psychiatry 7:e1134
Yu, Chenglong; Baune, Bernhard T; Licinio, Julio et al. (2017) A novel strategy for clustering major depression individuals using whole-genome sequencing variant data. Sci Rep 7:44389
Wong, M-L; Arcos-Burgos, M; Liu, S et al. (2017) The PHF21B gene is associated with major depression and modulates the stress response. Mol Psychiatry 22:1015-1025
Yu, Chenglong; Baune, Bernhard T; Licinio, Julio et al. (2017) Whole-genome single nucleotide variant distribution on genomic regions and its relationship to major depression. Psychiatry Res 252:75-79
Wong, Ma-Li; Dong, Chuanhui; Flores, Deborah L et al. (2014) Clinical outcomes and genome-wide association for a brain methylation site in an antidepressant pharmacogenetics study in Mexican Americans. Am J Psychiatry 171:1297-309
Berman, Steven M; Paz-Filho, Gilberto; Wong, Ma-Li et al. (2013) Effects of leptin deficiency and replacement on cerebellar response to food-related cues. Cerebellum 12:59-67
Wong, M-L; Dong, C; Andreev, V et al. (2012) Prediction of susceptibility to major depression by a model of interactions of multiple functional genetic variants and environmental factors. Mol Psychiatry 17:624-33
Ishibashi, K; Berman, S M; Paz-Filho, G et al. (2012) Dopamine D2/D3 receptor availability in genetically leptin-deficient patients after long-term leptin replacement. Mol Psychiatry 17:352-3
London, Edythe D; Berman, Steven M; Chakrapani, Shruthi et al. (2011) Short-term plasticity of gray matter associated with leptin deficiency and replacement. J Clin Endocrinol Metab 96:E1212-20
Pottier, N; Paugh, S W; Ding, C et al. (2010) Promoter polymorphisms in the ?-2 adrenergic receptor are associated with drug-induced gene expression changes and response in acute lymphoblastic leukemia. Clin Pharmacol Ther 88:854-61

Showing the most recent 10 out of 42 publications