Aims: Pharmacogenetic based dosing recommendations are provided in FDA-approved warfarin label for Caucasians. Evidence of notable difference in dosing algorithms of under-represented populations forced us to explore the genetic variability of CYP4F2 gene in Roma and Hungarian populations.
Patients And Methods: 484 Roma, 493 Hungarian untreated subjects were genotyped for the CYP4F2*3 (rs2108622) variant by PCR-RFLP assay.
Results And Discussion: We firstly report, that frequencies of the CYP4F2 rs2108622 GG, GA, AA genotypes and A allele in the Roma population were 46.5%, 42.6%, 10.9% and 32.2%; in Hungarians 50.1%, 42.2%, 7.7% and 22.8%, respectively. Bearing of two minor alleles of CYP4F2 missense variant (AA genotype) modestly explains inter-ethnic differences of studied populations (p<0.08). CYP4F2*3 (V433M) risk allele frequency of Roma (0.32) was in higher range, and of Hungarians (0.23) in lower range, as compared with other world populations.
Conclusions: Roma have an elevated chance for higher mean warfarin dose, besides a decreased risk of major bleeding events in long-term warfarin use.
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http://dx.doi.org/10.1016/j.etap.2015.05.008 | DOI Listing |
Sci Rep
December 2024
National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.
Inter-individual variability in drug responses is significantly influenced by genetic factors, underscoring the importance of population-specific pharmacogenomic studies to optimize clinical outcomes. In this study, we analyzed whole genome sequencing data from 949 unrelated Thai individuals and conducted an in-depth analysis of 3239 genes involved in drug pharmacokinetics, pharmacodynamics, or immune-mediated adverse drug reactions. We identified 43 single nucleotide polymorphisms (SNPs), 134 diplotypes, and 15 human leukocyte antigen (HLA) alleles, all with moderate to high clinical significance.
View Article and Find Full Text PDFPharmazie
August 2024
Laboratory of Clinical Pharmacy, Faculty of Pharmacy, Takasaki University of Health and Welfare; Education Center for Clinical Pharmacy, Faculty of Pharmacy, Takasaki University of Health and Welfare.
Renal function significantly influences the appropriate warfarin dosage. However, studies investigating the impact of genetic factors on warfarin dosage, considering renal function, are limited. This study aimed to assess the role of genetic polymorphisms in , , , , , and in warfarin dosage adjustment considering renal function.
View Article and Find Full Text PDFBiochem Genet
June 2024
Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), School of Life Sciences, Ministry of Education, Northwest University, #229 North TaiBai Road, Xi'an, Shaanxi, 710069, China.
Drug Metab Dispos
October 2024
Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (D.K.S., D.A., B.P.); and Department of Chemistry, Washington State University, Pullman, Washington (D.R.D.)
Protein abundance data of drug-metabolizing enzymes and transporters (DMETs) are useful for scaling in vitro and animal data to humans for accurate prediction and interpretation of drug clearance and toxicity. Targeted DMET proteomics that relies on synthetic stable isotope-labeled surrogate peptides as calibrators is routinely used for the quantification of selected proteins; however, the technique is limited to the quantification of a small number of proteins. Although the global proteomics-based total protein approach (TPA) is emerging as a better alternative for large-scale protein quantification, the conventional TPA does not consider differential sequence coverage by identifying unique peptides across proteins.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
March 2024
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington 98195, United States.
This study evaluated the underlying mechanistic links between genetic variability in vitamin K metabolic pathway genes ( and ) and phylloquinone hydroxylation activity using genotype- and haplotype-based approaches. Specifically, we characterized genetic variability in the locus and compared common single allele genotypes and common haplotypes as predictors of hepatic gene expression, enzyme abundance, and phylloquinone (VK) ω-hydroxylation kinetics. We measured and mRNA levels, CYP4F2 and CYP4F11 protein abundances, and the VK concentration-dependent ω-hydroxylation rate in matched human liver nucleic acid and microsome samples, utilizing a novel population modeling approach.
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