Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
Thiopurines are widely used as anticancer and immunosuppressive agents. However, life-threatening myelotoxicity has been noticed and largely explained by genetic variations, including NUDT15 polymorphisms (e.g., rs116855232). In this study, we conduct a meta-analysis to investigate the impact of rs116855232 on thiopurines-induced myelotoxicity susceptibility (1752 patients from 7 independent cohorts), as well as on thiopurines intolerance dose (2745 patients from 13 cohorts). Variant allele of rs116855232 contributes 7.86-fold (P < 0.00001, 95% CI: 6.13-10.08) higher risk to develop leucopenia with high specificity (91.74%) and sensitivity (43.19%), and lower thiopurines intolerance dose (P < 0.00001). Through bioinformatics prediction, amino acid changes induced by genetic variants are considered to reduce the stability, and break an α helix of NUDT15, which is part of the thiopurine binding pocket. Additionally, we conduct an expression quantitative trait loci (eQTL) analysis for NUDT15, and find a promoter-located eQTL signal (rs554405994), which may act as a potential marker to predict thiopurines-induced myelotoxicity. In conclusion, genetic polymorphisms in NUDT15 are strongly associated with adverse drug reaction (ADR) of thiopurines, although more evidences are needed to determine values of all functional NUDT15 polymorphisms for clinical regimen, rs116855232 should be considered as a highly credible pharmacogenetic indicator for thiopurines using espcially is Asians.
Pubmed ID: 28088792
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Database and central repository for genetic, genomic, molecular and cellular phenotype data and clinical information about people who have participated in pharmacogenomics research studies. The data includes, but is not limited to, clinical and basic pharmacokinetic and pharmacogenomic research in the cardiovascular, pulmonary, cancer, pathways, metabolic and transporter domains. PharmGKB welcomes submissions of primary data from all research into genes and genetic variation and their effects on drug and disease phenotypes. PharmGKB collects, encodes, and disseminates knowledge about the impact of human genetic variations on drug response. They curate primary genotype and phenotype data, annotate gene variants and gene-drug-disease relationships via literature review, and summarize important PGx genes and drug pathways. PharmGKB is part of the NIH Pharmacogenomics Research Network (PGRN), a nationwide collaborative research consortium. Its aim is to aid researchers in understanding how genetic variation among individuals contributes to differences in reactions to drugs. A selected subset of data from PharmGKB is accessible via a SOAP interface. Downloaded data is available for individual research purposes only. Drugs with pharmacogenomic information in the context of FDA-approved drug labels are cataloged and drugs with mounting pharmacogenomic evidence are listed.
View all literature mentionsGoogle Scholar provides a simple way to broadly search for scholarly literature. From one place, you can search across many disciplines and sources: articles, theses, books, abstracts and court opinions, from academic publishers, professional societies, online repositories, universities and other web sites. Google Scholar helps you find relevant work across the world of scholarly research. Features of Google Scholar * Search diverse sources from one convenient place * Find articles, theses, books, abstracts or court opinions * Locate the complete document through your library or on the web * Learn about key scholarly literature in any area of research How are documents ranked? Google Scholar aims to rank documents the way researchers do, weighing the full text of each document, where it was published, who it was written by, as well as how often and how recently it has been cited in other scholarly literature. * Publishers - Include your publications in Google Scholar * Librarians - Help patrons discover your library''s resources
View all literature mentionsSoftware application designed to facilitate viewing of local association results together with useful information about a locus, such as the location and orientation of the genes it includes, linkage disequilibrium coefficients and local estimates of recombination rates. It was developed by popular demand, as a result of many questions we have had about How did you make the figures in your talk? or How did you make the figures for your GWAS paper? (entry from Genetic Analysis Software)
View all literature mentions