ABCC1, ABCG2 and FOXP3: Predictive Biomarkers of Toxicity from Methotrexate Treatment in Patients Diagnosed with Moderate-to-Severe Psoriasis

BackgroundHigh-dose methotrexate (HD-MTX) is commonly employed in the treatment of malignant tumors in children and young adults due to its distinctive therapeutic efficacy. Nonetheless, the systemic exposure to MTX often results in liver injury (drug induced liver injury, DILI), thereby imposing limitations on the sustained administration of HD-MTX. Additionally, individual variations including genetic underpinnings attributable to disparities in therapeutic effects and clinical toxicity remain to be elucidated.MethodsA total of 374 patients receiving initial HD-MTX treatment were selected for this study, which aimed to establish a predictive model using binary logistic regression and a visual nomogram for DILI risk assessment. Demographic and clinical characteristics were collected at baseline and post-HD-MTX to explore their correlations with the occurrence of DILI. Additionally, genotyping of 25 single nucleotide polymorphisms from drug transporters and enzymes in the folic acid cycle was performed.ResultG allele mutation in ABCB1 rs1128503, *1b/*1b and *1b/*15 haplotypic mutation in SLCO1B1, female gender, and MTX dosage were identified as independent factors for moderate/severe DILI. Patients with GA or AA genotype in ABCB1 rs1128503 showed significant higher 24h MTX concentration than GG, and those with *1b/*1b haplotype group in SLCO1B1 exhibited lower dose adjusted concentration (C/D) than *1a/*1a group. Besides, patient administrated with HD-MTX were more prevalent to have higher C/D levels when using intravenous plus triple intrathecal injection route than those who were using intravenous injection alone. The composite predictive model (ROC curve: AUC = 0.805), comprising above four factors and 24h MTX concentration, exhibited high accuracy.ConclusionFemale gender, recessive mutation in ABCB1 rs1128503, and a range of MTX concentration may be risk factors for increased susceptibility to DILI. Conversely, the *1b/*1b and *1b/*15 mutations in SLCO1B1 may have a protective effect against DILI. The proposed predictive model facilitates early individual risk assessment, enabling the implementation of proactive prevention strategies.

show abstract

A Paradigm Shift on Emergence of Pharmacogenomics in the Era of Personalized Medicine

Kukreti,

Lamba,

Pant

et al. 2024

Advances in Medical Technologies and Clinical Practice

View full text Add to dashboard Cite

Pharmacogenomics is the study of genetic modifications in patients that influence their potential to metabolize medications, encouraging their tolerability and desired effect. Genetic (like genome-wide association & candidate gene) methods may help in choosing the most suitable drug and dosage, by impeding adverse drug reactions (ADRs). Pharmacogenomics are usually documented as key steps in personalized medicine. The significance of personalized medicine in healthcare is developing due to its defined genetic and molecular basis. Personalized medicine anticipates the beneficial or serious side effects of a medication by using specific individual's genetic profile. In the recent year's pharmacogenomics approaches are being widely used in personalizing therapies for diseases like Cancer, Rheumatoid arthritis, Asthma, Type-1 diabetes and many psychiatric disorders (depression, psychosis, schizophrenia etc.).This chapter provides an overview of the present importance of pharmacogenomics and identifies the challenges that need to be conquered for effective personalized medicine.

show abstract

ABCC1, ABCG2 and FOXP3: Predictive Biomarkers of Toxicity from Methotrexate Treatment in Patients Diagnosed with Moderate-to-Severe Psoriasis

Cited by 3 publications

References 85 publications

Synergistic chemo-photodynamic therapy based on hollow mesoporous organosilica nanoparticles for reducing psoriasis-like inflammation

Synergistic chemo-photodynamic therapy based on hollow mesoporous organosilica nanoparticles for reducing psoriasis-like inflammation

Integration of genomics, clinical characteristics and baseline biological profiles to predict the risk of liver injury induced by high-dose methotrexate

A Paradigm Shift on Emergence of Pharmacogenomics in the Era of Personalized Medicine

Contact Info

Product

Resources

About