Human Leukocyte Antigen (HLA) variants can be a risk factor for developing potentially fatal drug hypersensitivity reactions. Our aim was to estimate the potential impact of genotyping for the HLA risk alleles incorporated in the Dutch Pharmacogenetics Working Group (DPWG) guidelines in The Netherlands. We estimated the number of hypersensitivity reactions and associated deaths that can be avoided annually by genotyping for these HLA risk alleles. Additionally, the cost-effectiveness was estimated. Nationwide implementation of genotyping HLA risk alleles before initiating drugs with an actionable drug-gene interaction can potentially save the life of seven allopurinol initiators and two flucloxacillin initiators each year in The Netherlands. Besides these deaths, 28 cases of abacavir hypersensitivity, 24 cases of allopurinol induced SCARs, 6 cases of carbamazepine induced DRESS and 22 cases of flucloxacillin induced DILI can be prevented. Genotyping in abacavir initiators has a number needed to genotype of 31 to prevent one case of abacavir hypersensitivity and is cost-saving. Genotyping in allopurinol initiators has a number needed to genotype of 1149 to prevent one case of SCAR but is still cost-effective. Genotyping before initiating antiepileptic drugs or flucloxacillin is not cost-effective. Our results confirm the need for mandatory testing of in abacavir initiators, as indicated in the drug label, and show genotyping of 5801 in allopurinol initiators should be considered.
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http://dx.doi.org/10.3390/ph15010004 | DOI Listing |
J Clin Med
December 2024
Department of Endocrinology and Metabolic Diseases, Polish Mother's Memorial Hospital-Research Institute, 281/289 Rzgowska St., 93-338 Lodz, Poland.
: Severe COVID-19 still constitutes an important health problem. Taking into account the crucial role of HLA in immune reactions, evaluation of the impact of HLA on COVID-19 risk and clinical course seemed necessary, as the already available data are inconsistent. The aim of the present study was to compare the HLA profiles of patients with symptomatic SARS-CoV-2 infection and a healthy control group, as well as to compare HLA allele frequencies in patients with severe and non-severe courses of COVID-19.
View Article and Find Full Text PDFHum Immunol
January 2025
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:
Background: It has been demonstrated that COVID-19 vaccines confer significant protection, but temporal decay in the vaccine-induced antibodies has been reported; therefore, a third booster dose was considered. Human leukocyte antigen (HLA) class II molecules act as antigen presenting structures, play critical roles in the formation of an efficient antibody response. The current study aimed to evaluate the anti-receptor binding domain (RBD) antibody response after the booster dose of SpikoGen® vaccine in individuals with a history of Sinopharm primary vaccination series and its association with HLA-DQB1 and -DRB alleles.
View Article and Find Full Text PDFBMC Immunol
January 2025
Laboratoire Génomique, Bioinformatique, et Chimie Moléculaire, Conservatoire National des Arts et Métiers, 2 rue Conté 75003, Paris, EA7528, France.
Introduction: We have reanalyzed the genomic data from the International Collaboration for the Genomics of HIV (ICGH), focusing on HIV-1 Elite Controllers (EC).
Methods: A genome-wide association study (GWAS) was performed, comparing 543 HIV-1 EC individuals with 3,272 uninfected controls (CTR) of European ancestry. 8 million single nucleotide polymorphisms (SNPs) and HLA class I and class II gene alleles were imputed to compare EC and CTR.
Nihon Yakurigaku Zasshi
January 2025
Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development.
Allergen-specific immunotherapy (AIT) has been a longstanding treatment for allergic diseases. Historically, subcutaneous immunotherapy was the main approach, but with the development of sublingual preparations, which are associated with fewer systemic side effects, sublingual immunotherapy is gaining global popularity. In Japan, the approval of standardized sublingual immunotherapy preparations in 2014 has significantly accelerated its adoption.
View Article and Find Full Text PDFSci Rep
January 2025
NMC Genetics India Pvt. Ltd., Gurugram, Haryana, 122001, India.
Rising cases of type 2 diabetes (T2D) in India, especially in metropolitan cities is an increasing concern. The individuals that were most affected are young professionals working in the corporate sector. However, the corporate sector has remained the least explored for T2D risk predisposition.
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