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Characterizing the genetic architecture of drug response using gene-context interaction methods.
Cell Genom
December 2024
Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Neurology, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Computational Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA. Electronic address:
Identifying factors that affect treatment response is a central objective of clinical research, yet the role of common genetic variation remains largely unknown. Here, we develop a framework to study the genetic architecture of response to commonly prescribed drugs in large biobanks. We quantify treatment response heritability for statins, metformin, warfarin, and methotrexate in the UK Biobank.
View Article and Find Full Text PDFAssociation of Gene Polymorphisms and Its Regulatory miRNAs with Methotrexate Toxicity in Children with Acute Lymphoblastic Leukemia.
Curr Issues Mol Biol
October 2024
Pediatric & Adolescent Hematology Oncology Unit, 2nd Pediatric Department Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA Hospital, S. Kiriakidi 1, 54636 Thessaloniki, Greece.
Methotrexate (MTX) is an anti-folate chemotherapeutic agent that is considered to be a gold standard in Acute Lymphoblastic Leukemia (ALL) therapy. Nevertheless, toxicities induced mainly due to high doses of MTX are still a challenge for clinical practice. MTX pharmacogenetics implicate various genes as predictors of MTX toxicity, especially those that participate in MTX intake like ().
View Article and Find Full Text PDFFrequency of pharmacogenomic variants affecting safety and efficacy of immunomodulators and biologics in a South Asian population from Sri Lanka.
Hum Genomics
September 2024
Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka.
Article Synopsis
- - The study analyzed genetic polymorphisms in Sri Lankans to understand variations in responses to immunomodulator drugs used for autoimmune diseases and blood cancers, using data from 670 participants.
- - Among the most common variants, SLC19A1 showed a major presence at 63.3%, while others had varying frequencies, indicating significant genetic diversity compared to global populations.
- - Notably, some variants like MTHFR were less prevalent in Sri Lankans compared to other groups, highlighting unique genetic profiles that could influence drug efficacy and safety in this population.
Genetic polymorphisms and their association with methotrexate polyglutamates during maintenance treatment in Korean children and young adults with acute lymphoblastic leukemia.
Eur J Pharm Sci
November 2024
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address:
Article Synopsis
- The study aimed to examine how genetic differences affect the metabolism of methotrexate (MTX) in Korean children and young adults with acute lymphoblastic leukemia, particularly looking at MTX polyglutamates (MTX-PGs) in red blood cells.
- Researchers included patients on a standard MTX maintenance therapy and analyzed levels of various MTX-PGs, genetic polymorphisms related to MTX metabolism, and their associations.
- Significant findings revealed that 14 genetic polymorphisms correlated with different MTX-PG levels, highlighting the potential for personalized treatment strategies based on individual genetic profiles in leukemia therapy.
Impact of MTHFR gene polymorphism on the outcome of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients.
Sci Rep
July 2024
Department of Biochemistry and Clinical Laboratory Science, College of Pharmacy, University of Baghdad, Baghdad, Iraq.
Analyze the relationship between genetic variations in the MTHFR gene at SNPs (rs1801131 and rs1801133) and the therapy outcomes for Iraqi patients with rheumatoid arthritis (RA). The study was conducted on a cohort of 95 RA Iraqi patients. Based on their treatment response, the cohort was divided into two groups: the responder (47 patients) and the nonresponder (48 patients), identified after at least three months of methotrexate (MTX) treatment.
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