Friday 2 March 2012
Methotrexate is used to treat autoimmune diseases and malignancies, including acute lymphoblastic leukemia (ALL).
Inter-individual variation in clearance of methotrexate results in heterogeneous systemic exposure, clinical efficacy, and toxicity.
In a genome-wide association study of children with ALL, SLCO1B1 have been identified as harboring multiple common polymorphisms associated with methotrexate clearance.
The extent of influence of rare versus common variants on pharmacogenomic phenotypes remains largely unexplored.
Rare variants are likely to have an important effect on pharmacogenetic phenotypes.
- Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition. Ramsey LB, Bruun GH, Yang W, Treviño LR, Vattathil S, Scheet P, Cheng C, Rosner GL, Giacomini KM, Fan Y, Sparreboom A, Mikkelsen TS, Corydon TJ, Pui CH, Evans WE, Relling MV. Genome Res. 2012 Jan;22(1):1-8. PMID: 22147369