Methotrexate (MTX), one of the important disease-modifying anti-rheumatic drugs, is the first-line drug for rheumatoid arthritis (RA) treatment. However, its adverse drug effects (ADEs) often lead to the abortion of MTX therapy. Human organic anion-transporting polypeptide 1A2 (OATP1A2, also referred as OATP-A or OATP1) encoded by SLCO1A2 gene is an important isoform of the solute carrier transporter (SLC) family. It is known to participate in the cellular uptake of MTX. In our previous study, we identified four OATP1A2 natural variants (E184K, D185N, T259P, and D288N) with impaired MTX uptake activity. This study aimed to evaluate the association of the SLCO1A2 genetic variations encoding these OATP1A2 variants and MTX-related toxicity in RA patients. A total of 60 RA patients were genotyped for these four polymorphisms (G550A, G553A, A775C, and G862A). The association between SLCO1A2 genetic variations and MTX toxicity was analyzed by binary logistic regression analysis. Single nucleotide polymorphisms (SNPs) analysis revealed that A775C and G862A SNPs were not detected in RA patients enrolled in this study, and the presence of 550AA genotype was associated with a high risk of MTX ADEs. Haplotype analysis revealed that H3 (H3 = AG) showed a high risk of MTX ADEs. Furthermore, there was a significant association of 550AA genotype and impaired MTX disposition, which might be the cause of the increased incidence of MTX ADEs in RA patients. Therefore, genetic variations in SLCO1A2 gene are risk factors for MTX toxicity and its information contributes to the prediction of MTX-related toxicity in RA treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/jbt.22513 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes.
Nat Commun
September 2024
Penn Neurodegeneration Genomics Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Progressive supranuclear palsy (PSP), a rare Parkinsonian disorder, is characterized by problems with movement, balance, and cognition. PSP differs from Alzheimer's disease (AD) and other diseases, displaying abnormal microtubule-associated protein tau by both neuronal and glial cell pathologies. Genetic contributors may mediate these differences; however, the genetics of PSP remain underexplored.
View Article and Find Full Text PDFThe Induction of Drug Uptake Transporter Organic Anion Transporting Polypeptide 1A2 by Radiation Is Mediated by the Nonreceptor Tyrosine Kinase v-YES-1 Yamaguchi Sarcoma Viral Oncogene Homolog 1.
Drug Metab Dispos
October 2024
College of Life Sciences, South China Agricultural University, Guangzhou, China (Z.W., J.Y., K.L., X.W., Z.Z., M.H.); and Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, South China Agricultural University, Guangzhou, China(M.H.)
Organic anion transporting polypeptides (OATP, gene symbol ) are well-recognized key determinants for the absorption, distribution, and excretion of a wide spectrum of endogenous and exogenous compounds including many antineoplastic agents. It was therefore proposed as a potential drug target for cancer therapy. In our previous study, it was found that low-dose X-ray and carbon ion irradiation both upregulated the expression of OATP family member OATP1A2 and in turn, led to a more dramatic killing effect when cancer cells were cotreated with antitumor drugs such as methotrexate.
View Article and Find Full Text PDFWhole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy.
Mol Neurodegener
August 2024
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Article Synopsis
- Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease linked to abnormal tau protein accumulation, and previous studies were limited in exploring rare genetic variants due to the use of genotype arrays.* -
- In this study, whole genome sequencing (WGS) on a large cohort allowed researchers to confirm known genetic loci related to PSP and discover new associations, particularly highlighting a different role for the APOE ε2 allele compared to Alzheimer's disease.* -
- The findings expand knowledge of PSP's genetic underpinnings and identify potential targets for future research into the disease's mechanisms and treatments.*
Risk Variants Associated With Normal Pressure Hydrocephalus: Genome-Wide Association Study in the FinnGen Cohort.
Neurology
September 2024
From the Department of Neurosurgery (J. Räsänen, K.M., V.E.K., M.O., J.E.J., V.L.), Kuopio University Hospital and Institute of Clinical Medicine-Neurosurgery, and Institute of Biomedicine (S. Heikkinen, K.M., A.L., T.K., M.H.), University of Eastern Finland, Kuopio; Institute for Molecular Medicine Finland (FIMM) (J.M., A.P.), Helsinki Institute of Life Science (HiLIFE), University of Helsinki; Department of Neurology (A.J.), Clinical Neurosciences, Helsinki University Hospital and University of Helsinki, Finland; Univ. Lille (B.G.-B., C.B., J.-C.L.), Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, France; Department of Neurosurgery (M.O., K.L., J.S.), University of Helsinki and Helsinki University Hospital; Clinical Neurosciences (C.A., J.F., A.K., J. Rinne), Department of Neurosurgery, University of Turku and Turku University Hospital; Department of Neurosurgery (A.R.), Tampere University Hospital; Unit of Clinical Neuroscience (M.K., M.v.u.z.F.), Neurosurgery, University of Oulu and Medical Research Center, Oulu University Hospital; Finnish Institute for Health and Welfare (THL) (M.P.); University of Helsinki (M.P.); Department of Neurosciences (A.M.K., A.M.P.), University of Helsinki; Department of Geriatrics (A.M.K.), Helsinki University Hospital; NeuroCenter (A.M.K.), Kuopio University Hospital; Institute of Clinical Medicine-Neurology (V.J., H.S.), University of Eastern Finland; School of Medicine (A.M.), Institute of Clinical Medicine, Pathology and Forensic Medicine, and Translational Cancer Research Area, University of Eastern Finland; Department of Clinical Pathology (A.M.), Kuopio University Hospital; Unit of Clinical Medicine (S. Helisalmi), University of Eastern Finland, Kuopio, Finland; Department of Neurosurgery (P.K.E.), Oslo University Hospital-Rikshospitalet; Institute of Clinical Medicine (P.K.E.), Faculty of Medicine, and KG Jebsen Centre for Brain Fluid Research (P.K.E.), University of Oslo, Norway; Analytical and Translational Genetics Unit (A.P., M.I.K.), Department of Medicine, Massachusetts General Hospital, Boston; Program in Medical and Population Genetics (A.P., M.I.K.), and Stanley Center for Psychiatric Research (A.P., M.I.K.), Broad Institute for Harvard and MIT, Cambridge, MA.
Background And Objectives: Large-scale genome-wide studies of chronic hydrocephalus have been lacking. We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH).
Methods: We used a case-control study design implementing FinnGen data containing 473,691 Finns with genotypes and nationwide health records.
Genome-wide associations with longevity and reproductive traits in U.S. rangeland ewes.
Front Genet
May 2024
Department of Animal, Veterinary and Food Sciences, University of Idaho, Moscow, ID, United States.
Improving ewe longevity is an important breeding and management goal, as death loss and early culling of mature ewes are economic burdens in the sheep industry. Ewe longevity can be improved by selecting for positive reproductive outcomes. However, the breeding approaches for accomplishing this come with the challenge of recording a lifetime trait.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!