The impact of single nucleotide polymorphisms in <i>ADORA2A</i> and <i>ADORA3</i> genes on the early response to methotrexate and presence of therapy side effects in children with juvenile idiopathic arthritis: Results of a preliminary study

Roszkiewicz, Justyna; Michałek, Dominika; Рык, А. А.; Swacha, Zbigniew; Szmyd, Bartosz; Smolewska, Elżbieta

doi:10.1111/1756-185x.13972

Cited by 9 publications

(5 citation statements)

References 26 publications

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“…37,38 Adenosine was identified as a compound which modulates the effects of adrenoreceptors, and certain medications utilized in the treatment of psoriasis affect concentrations of adenosine, such as methotrexate. 39 However, there are limited studies evaluating how ADRA1B variants in patients affect responses to these medications, identifying an area of potential research. Of note, the priority index identified ADRA1B as a gene with a strong association with PsA as well, however, limited clinical data is currently available on the significance of this association and further research is needed.…”

Section: Psoriasismentioning

confidence: 99%

Identifying Novel Psoriatic Disease Drug Targets Using a Genetics-Based Priority Index Pipeline

Bui

Liu

Hong

et al. 2021

Journal of Psoriasis and Psoriatic Arthritis

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Background: Despite numerous genome-wide association studies conducted in psoriasis and psoriatic arthritis, only a small fraction of the identified genes has been therapeutically targeted. Objective: We sought to identify and analyze potential therapeutic targets for psoriasis and psoriatic arthritis (PsA) using the priority index (Pi), a genetics-dependent drug target prioritization approach. Methods: Significant genetic variants from GWAS for psoriasis, PsA, and combined psoriatic disease were annotated and run through the Pi pipeline. Potential drug targets were identified based on genomic predictors, annotation predictors, pathway enrichment, and pathway crosstalk. Results: Several gene targets were identified for psoriasis and PsA that demonstrated biological associations to their respective diseases. Some are currently being explored as potential therapeutic targets (i.e. ICAM1, NF-kB, REV3 L, ADRA1B for psoriasis; CCL11 for PsA); others have not yet been investigated (i.e. LNPEP, LCE3 for psoriasis; UBLCP1 for PsA). Additionally, many nodal points of potential intervention were identified as promising therapeutic targets. Of these, some are currently being studied such as TYK2 for psoriasis, and others have yet to be explored (i.e. PPP2CA, YAP1, PI3 K, AKT, FOXO1, RELA, CSF2, IFNGR1, IFNGR2 for psoriasis; GNAQ, PLCB1, GNAI2 for PsA). Conclusion: Through Pi, we identified data-driven candidate therapeutic gene targets and pathways for psoriasis and PsA. Given the sparse PsA specific genetic studies and PsA specific drug targets, this analysis could prove to be particularly valuable in the pipeline for novel psoriatic therapies.

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Section: Psoriasismentioning

confidence: 99%

Identifying Novel Psoriatic Disease Drug Targets Using a Genetics-Based Priority Index Pipeline

Bui

Liu

Hong

et al. 2021

Journal of Psoriasis and Psoriatic Arthritis

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“…In the literature, there are no studies investigating the link between genetic variants and pegasparaginase-induced hepatotoxicity. 39 Patient 6 carried a heterozygote variant in miR-4481 (rs7896283, A > G), yet only the homozygote GG genotype has been significantly associated with vinca alkaloid-induced neurotoxicity. 13 This patient developed a vocal cord paresis after a single vincristine administration.…”

Section: Vinca Alkaloid-induced Toxicitymentioning

confidence: 98%

“…In the literature, there are no studies investigating the link between genetic variants and pegasparaginase-induced hepatotoxicity. 39…”

Section: Vinca Alkaloid-induced Toxicitymentioning

confidence: 99%

Genetic variants found in paediatric oncology patients with severe chemotherapy-induced toxicity: A case series

Bernsen

Hanff

Haveman

et al. 2022

J Oncol Pharm Pract

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Paediatric oncology patients who develop severe chemotherapy-induced toxicity that requires dose reduction, delay or termination of treatment are at risk of decreased treatment efficacy. Previous research has provided evidence that genetic variants in TPMT, NUDT15, UGT1A1 and DPYD are associated with toxicity of anticancer drugs. This led to pharmacogenetic guidelines that are integrated into clinical practice in paediatric oncology. Recently, novel genetic variants have been associated with a higher risk of developing chemotherapy-induced toxicity. In this case series, we selected 21 novel variants and genotyped these in nine patients with excessive chemotherapy-induced toxicity using whole exome sequencing or micro-array data. We observed that six out of nine patients carried at least one variant that, according to recent studies, potentially increased the risk of developing methotrexate- or vincristine-induced toxicity. As patient-derived genetic data are becoming widely accessible in paediatric oncology, these variants could potentially enter clinical practice to mitigate chemotherapy-induced toxicity.

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“…MTX is frequently used in patients who are at an increased risk of mycosis. Indications for the use of MTX include acute lymphocytic leukemia in children, acute lymphoblastic and myeloid leukemia in adults, patients with breast, ovarian, cervical, testicular, lung, or bladder cancer, those with bone sarcoma, epithelium and chorionic adenoma, advanced mycosis fungoides, meningeal forms of leukemia and lymphoma, severe psoriasis, psoriatic arthritis, severe active rheumatoid arthritis, osteosarcoma, and non-Hodgkin's lymphoma (Abolmaali et al, 2013;Bello et al, 2017;Huennekens, 1994;Polańska et al, 2016;Roszkiewicz et al, 2020Roszkiewicz et al, , 2021. e cross-resistance between FCZ and MTX is mediated through the overexpression of CaMDR1 gene, which encodes an MFS protein (Ben-Yaacov et al, 1994;Jensen, 2016;Kohli et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Detection of Cross-Resistance Between Methotrexate and Azoles in Candida albicans and Meyerozyma guilliermondii: An In Vitro Study

2021

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In recent years, there has been a rapid increase in the incidence of Candida infections. The different species of the genus Candida vary in their virulence abilities and susceptibility to antifungal agents, depending on several external factors. The result of such modifications may be cross-resistance, which is understood as an acquired resistance to a certain antimicrobial agent after exposure to another drug. The aim of this study was to determine the possibility of cross-resistance between fluconazole, voriconazole, itraconazole, and methotrexate in Candida albicans and Meyerozyma guilliermondii (syn. Candida guilliermondii ). Fifteen strains of M. guilliermondii and eight strains of C. albicans , including the standard strains, were tested. For all strains, the minimum inhibitory concentrations (MICs) for fluconazole, voriconazole, and itraconazole were determined before and after stimulation with methotrexate. The median MICs in M. guilliermondii before and after stimulation were 9.333 and 64 mg/L ( p = 0.005) for fluconazole; 0.917 and 1.667 mg/L ( p = 0.001) for itraconazole, respectively. No significant change in MIC was observed for voriconazole. For C. albicans strains, the median MICs before and after stimulation were 0.917 and 64 mg/L ( p = 0.012) for fluconazole; 0.344 and 1.135 mg/L ( p = 0.018) for voriconazole, respectively. There was no significant change in MIC values for itraconazole. Thus, this study demonstrates the presence of cross-resistance between voriconazole, itraconazole, fluconazole, and methotrexate for the selected strains. Methotrexate exposure induces different responses when certain drugs are used for various species. Therefore, if a patient was previously exposed to methotrexate, there may be a higher risk of treatment failure with fluconazole than with other azoles such as voriconazole for fungemia caused by M. guilliermondii or itraconazole for C. albicans infection.

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The impact of single nucleotide polymorphisms in ADORA2A and ADORA3 genes on the early response to methotrexate and presence of therapy side effects in children with juvenile idiopathic arthritis: Results of a preliminary study

Cited by 9 publications

References 26 publications

Identifying Novel Psoriatic Disease Drug Targets Using a Genetics-Based Priority Index Pipeline

Identifying Novel Psoriatic Disease Drug Targets Using a Genetics-Based Priority Index Pipeline

Genetic variants found in paediatric oncology patients with severe chemotherapy-induced toxicity: A case series

Detection of Cross-Resistance Between Methotrexate and Azoles in Candida albicans and Meyerozyma guilliermondii: An In Vitro Study

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