Genome-wide study identifies association between HLA-B*55:01 and penicillin allergy

Krebs, Kristi; Bovijn, Jonas; Lepamets, Maarja; Jc, Censin; Jürgenson, Tuuli; Särg, Dage; Luo, Yang; Skotte, Line; Geller, Frank; Feenstra, Bjarke; Wang, W; Auton, Adam; Raychaudhuri, Soumya; Esko, Tõnu; Metspalu, Andres; Laur, Sven; Mv, Holmes; Cm, Lindgren; Mägi, Reedik; Milani, Lili; Fadista, João

doi:10.1101/2020.02.27.967497

Cited by 6 publications

(7 citation statements)

References 66 publications

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“…The only way to advance genetic research more quickly in this moment of urgency is to use cohorts for whom genetic data already exists. National biobanks such as the Spain and Italy biobanks used in one recent study 5 , have access to the most reliable clinical data and outcomes, whereas commercial providers such as 23andMe who have done their own study have greater numbers 6 but lack accurate clinical data.…”

Section: Introductionmentioning

confidence: 99%

Genetic risk factors for death with SARS-CoV-2 from the UK Biobank

Gam

Pandurangan

et al. 2020

Preprint

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We present here genetic risk factors for survivability from infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for coronavirus disease 19 (COVID-19). At the time of writing it is too early to determine comprehensively and without doubt all risk factors, but there is an urgency due to the global pandemic crisis that merits this early analysis. We have nonetheless discovered 5 novel risk variants in 4 genes, discovered by examining 193 deaths from 1,412 confirmed infections in a group of 5,871 UK Biobank participants tested for the virus. We also examine the distribution of these genetic variants across broad ethnic groups and compare it to data from the UK Office of National Statistics for increased risk of death from SARS-CoV-2. We confidently identify the gene ERAP2 with a high-risk variant, as well as three other genes of potential interest. Although mostly rare, a common theme of genetic risk factors affecting survival might be the inability to launch or modulate an effective immune and stress response to infection from the SARS-CoV-2 virus.

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Section: Introductionmentioning

confidence: 99%

Genetic risk factors for death with SARS-CoV-2 from the UK Biobank

Gam

Pandurangan

et al. 2020

Preprint

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“…34 An example is beta-lactam antibiotic anaphylaxis recently mapped to a single nucleotide polymorphism, of which the HLA-DQA1*01:05 loci is an example. 10,11,34,35 Other variants at the DBR1 site can be examined for their known role in perioperative radio-iodine contrast and latex anaphylaxis. 34,35 The depth of testing needed for resolution is shown by the presence of more than a single loci with polymorphisms that are involved in penicillin anaphylaxis with a common variant on HLA-B*55:01.…”

Section: Discussionmentioning

confidence: 99%

“…34,35 The depth of testing needed for resolution is shown by the presence of more than a single loci with polymorphisms that are involved in penicillin anaphylaxis with a common variant on HLA-B*55:01. 10,11 We propose protein testing to identify changes in Masrelated G protein-coupled receptor X2 (MRGPRX2) on mast cells, coded by chromosome 11. 12 This is one of the mechanisms where rocuronium, cis-atracurium, remifentanil, and morphine directly activate a variant receptor causing mast cell degranulation.…”

Section: Discussionmentioning

confidence: 99%

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Epidemiology of suspected life-threatening perioperative anaphylaxis: a cross-sectional multicentre study in China

Zhang

Liu

et al. 2022

British Journal of Anaesthesia

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“…One recent GWAS identified the intronic variant rs114892859, a tag SNP of HLA-B*55:01, as a strong predictor of penicillin allergy in a European population (OR=1.47, p=1.29*10 -29 ; ref. 34 ). Furthermore, the direct association between HLA-B*55:01 and penicillin allergy was corroborated in another independent cohort containing more than 1 million subjects of European ancestry (OR=1.3, p=1*10 -47 ).…”

Section: Key Examples Of Germline Pharmacogenomic Biomarkersmentioning

confidence: 99%

Pharmacogenomics in the era of next generation sequencing – from byte to bedside

Russell

Zhou

Almousa

et al. 2021

Drug Metabolism Reviews

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Pharmacogenetic research has resulted in the identification of a multitude of genetic variants that impact drug response or toxicity. These polymorphisms are mostly common and have been included as actionable information in the labels of numerous drugs. In addition to common variants, recent advances in Next Generation Sequencing (NGS) technologies have resulted in the identification of a plethora of rare and population-specific pharmacogenetic variations with unclear functional consequences that are not accessible by conventional forward genetics strategies. In this review, we discuss how comprehensive sequencing information can be translated into personalized pharmacogenomic advice in the age of NGS. Specifically, we provide an update of the functional impacts of rare pharmacogenetic variability and how this information can be leveraged to improve pharmacogenetic guidance. Furthermore, we critically discuss the current status of implementation of pharmacogenetic testing across drug development and layers of care. We identify major gaps and provide perspectives on how these can be minimized to optimize the utilization of NGS data for personalized clinical decision-support.

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Genome-wide study identifies association between HLA-B*55:01 and penicillin allergy

Abstract: 52

Cited by 6 publications

References 66 publications

Genetic risk factors for death with SARS-CoV-2 from the UK Biobank

Genetic risk factors for death with SARS-CoV-2 from the UK Biobank

Epidemiology of suspected life-threatening perioperative anaphylaxis: a cross-sectional multicentre study in China

Pharmacogenomics in the era of next generation sequencing – from byte to bedside

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