Tenofovir disoproxyl fumarate (TDF) has been associated with renal tubular abnormalities, phosphaturia and proteinuria (retinol binding protein, RBP, loss): vitamin D (VD) and PTH affect these markers. Aim was to understand if some single nucleotide polymorphisms (SNPs) were predictors of renal abnormalities in an Italian cohort of HIV-affected patients. DNA was analyzed through real-time PCR, urinary RBP corrected by creatinine (uRBP/Cr). The majority of patients received TDF. Abnormal uRBP/Cr was more frequent in TDF recipients: eGFR <90 mL/min and TDF were predictors in the whole cohort, whereas eGFR <90 mL/min, TDF concentrations and CYP24A1-3999TT in TDF-treated patients. Phosphate levels were higher low VD level patients: age <50 years, CYP27B1 + 2838CC genotype and non-European ancestry were predictors. PTH levels were border-line higher in TDF patients: non-European ancestry, females, TDF, VD levels < 30 ng/mL and SLC28A2-124CT/TT and ABCC2-24CC were predictors. For the first time, SNPs were associated with PTH, phosphate, calcium and tubular dysfunction in HIV-infected patients.
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http://dx.doi.org/10.1038/s41397-019-0109-x | DOI Listing |
Cureus
December 2024
Pulmonology and Critical Care, Marshall University Joan C. Edwards School of Medicine, Huntington, USA.
Malignant hyperthermia is a pharmacogenetic disorder that manifests clinically as a hypermetabolic crisis when a patient with a mutation in the ryanodine or dihydropyridine receptor genes is exposed to neuromuscular blocking agents. Depolarizing neuromuscular agents are known to cause malignant hyperthermia, but cases caused by nondepolarizing agents are rarely reported. We present a case consistent with malignant hyperthermia after receipt of cisatracurium, a nondepolarizing anesthetic agent.
View Article and Find Full Text PDFClin Drug Investig
January 2025
Pharmacy Department, Hamad Medical Corporation, Doha, 3050, Qatar.
Background And Objective: While standard doses of adjuvant fluoropyrimidine-based chemotherapies are generally safe for most patients, the risk of severe adverse drug reactions (ADRs) is increased for those with dihydropyrimidine dehydrogenase deficiency (DPYD), a genetic variation that affects drug metabolism. The objective of this study was to examine the cost effectiveness of offering DPYD pharmacogenetic-guided care, where genetic testing informs personalized dosing versus the current standard of care (SoC), which involves administering fluoropyrimidine-based therapies without prior genetic screening, for local or metastatic breast cancer patients in Qatar.
Methods: We developed a two-stage decision analysis, with an analytic tree model over a 6-month period, followed by a life-table Markov model over a lifetime horizon.
Clin Transplant
February 2025
Excellence Center for Organ Transplantation, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
Since 1987, King Chulalongkorn Memorial Hospital (KCMH) has performed a substantial number of heart transplants as a specific therapy for advanced-stage heart failure. This descriptive study aimed to analyze post-transplant survival in the recent era compared to earlier periods and examine the pharmacogenetics of related immunosuppressants. Data from all recipients who underwent heart transplants from 1987 to 2021 were retrospectively retrieved from the electronic medical record.
View Article and Find Full Text PDFBiochim Biophys Acta Gen Subj
January 2025
Institute of Clinical Pharmacology, University Hospital of RWTH Aachen, Aachen, Germany.
In vitro and ex vivo studies on drug metabolism and stability are vital for drug development and pre-clinical safety assessment. Traditional in vitro models, such as liver enzyme (S9) fractions and microsomes, often fail to account for individual variability. Personalized models, including 3D cell models and organoids, offer promising alternatives but may not fully replicate physiological processes, especially for Cytochrome P450 (CYP) families involved in extrahepatic metabolism.
View Article and Find Full Text PDFDig Liver Dis
January 2025
Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Laboratory Medicine, Region Jönköping County, Jönköping, Sweden. Electronic address:
Background: Azathioprine (AZA) is part of the standard treatment for autoimmune hepatitis (AIH). The first step in the complex bioconversion of AZA to active metabolites is mediated by glutathione transferases (GSTs).
Aims: Elucidate the association between GSTM1 and GSTT1 copy number variation (CNV), genetic variation in GSTA2, GSTP1, and inosine-triphosphate-pyrophosphatase, and the response to AZA in AIH.
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