Abstract
Our knowledge of genetic predisposing factors of drug hypersensitivity reactions (DHRs) is still scarce. The analysis of the genetic basis of these reactions may contribute to dissect the underlying mechanisms. We will outline current knowledge of the genetic predictors of most common DHRs, including reactions to betalactam antibiotics (BLs), nonsteroidal anti-inflammatory drugs (NSAIDs) and biological agents. The predictors of DHRs to BLs are mostly linked to IgE-class switching, IgE pathway and atopy (IL4R, NOD2, LGALS3) in replicated candidate gene studies, and to antigen presentation (HLA-DRA) in the single replicated GWAS performed so far. The HLA-DRA variants are predictors of allergy to penicillins, but not to cephalosporins and they influence also the sensitization against prevalent allergens. The predictors of DHRs against NSAIDs are mostly linked to metabolism of eicosanoids (ALOX5, ALOX5AP, TBXAS1, PTGDR, CYSLTR1). Single nucleotide polymorphisms (SNPs) in genes involved in histamine biosynthesis and antigen presentation, HLA, could also have a role in DHRs against NSAIDs. The intriguing association of DHRs to NSAIDs with atopy should deserve further attention. Predictors of DHRs against asparaginase and other biological agents relate to antigen presentation (HLA-DRB1 and HLA-A alleles, respectively). The potential relationship of genetic predictors of DHRs with pathomechanisms also involved in environmental exposure and atopy highlights the need to perform GWAS in contrasted populations, taking into account world-wide variations of allele frequencies and contrasted situations of environmental exposure.
Keywords: Hypersensitivity, immediate and non-immediate reactions, betalactams, nonsteroidal anti-inflammatory drugs, polymorphisms, candidate genes, genome-wide association study.
Current Pharmaceutical Design
Title:Genetic Predictors of Drug Hypersensitivity
Volume: 22 Issue: 45
Author(s): Jose A. Cornejo-Garcia, Abderrahim Oussalah, Miguel Blanca, Rosa-Maria Gueant-Rodriguez, Cristobalina Mayorga, Julie Waton, Annick Barbaud, Francesco Gaeta, Antonino Romano and Jean-Louis Gueant
Affiliation:
Keywords: Hypersensitivity, immediate and non-immediate reactions, betalactams, nonsteroidal anti-inflammatory drugs, polymorphisms, candidate genes, genome-wide association study.
Abstract: Our knowledge of genetic predisposing factors of drug hypersensitivity reactions (DHRs) is still scarce. The analysis of the genetic basis of these reactions may contribute to dissect the underlying mechanisms. We will outline current knowledge of the genetic predictors of most common DHRs, including reactions to betalactam antibiotics (BLs), nonsteroidal anti-inflammatory drugs (NSAIDs) and biological agents. The predictors of DHRs to BLs are mostly linked to IgE-class switching, IgE pathway and atopy (IL4R, NOD2, LGALS3) in replicated candidate gene studies, and to antigen presentation (HLA-DRA) in the single replicated GWAS performed so far. The HLA-DRA variants are predictors of allergy to penicillins, but not to cephalosporins and they influence also the sensitization against prevalent allergens. The predictors of DHRs against NSAIDs are mostly linked to metabolism of eicosanoids (ALOX5, ALOX5AP, TBXAS1, PTGDR, CYSLTR1). Single nucleotide polymorphisms (SNPs) in genes involved in histamine biosynthesis and antigen presentation, HLA, could also have a role in DHRs against NSAIDs. The intriguing association of DHRs to NSAIDs with atopy should deserve further attention. Predictors of DHRs against asparaginase and other biological agents relate to antigen presentation (HLA-DRB1 and HLA-A alleles, respectively). The potential relationship of genetic predictors of DHRs with pathomechanisms also involved in environmental exposure and atopy highlights the need to perform GWAS in contrasted populations, taking into account world-wide variations of allele frequencies and contrasted situations of environmental exposure.
Export Options
About this article
Cite this article as:
Cornejo-Garcia A. Jose, Oussalah Abderrahim, Blanca Miguel, Gueant-Rodriguez Rosa-Maria, Mayorga Cristobalina, Waton Julie, Barbaud Annick, Gaeta Francesco, Romano Antonino and Gueant Jean-Louis, Genetic Predictors of Drug Hypersensitivity, Current Pharmaceutical Design 2016; 22 (45) . https://dx.doi.org/10.2174/1381612822666160927114941
DOI https://dx.doi.org/10.2174/1381612822666160927114941 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Current Options for the Pharmacotherapy of Obesity
Current Pharmaceutical Design Aspirin Intolerance: Experimental Models for Bed-to-Bench
Current Drug Targets Mosquito Allergy and Mosquito Salivary Allergens
Protein & Peptide Letters Immediate and Late Adverse Reactions to Iodinated Contrast Media: A Pharmacological Point of View
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Cold-induced Anaphylaxis: The Case of a 9-year-old Child and Review of the Literature
Endocrine, Metabolic & Immune Disorders - Drug Targets Antineoplastic Activities, Apoptotic Mechanism of Action and Structural Properties of a Novel Silver(I) Chelate
Current Medicinal Chemistry Cross-Reactivity in Cell-Mediated and IgE-Mediated Hypersensitivity to Glucocorticoids
Current Pharmaceutical Design The Role of Antihistamine Drugs in Allergic Disorders
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Future Preventive and Therapeutic Targets for Transfusion-Related Acute Lung Injury
Current Pharmaceutical Design Extracellular Proteases as Targets for Drug Development
Current Protein & Peptide Science Nutraceuticals - An Emerging Era in the Treatment and Prevention of Cardiovascular Diseases
Current Pharmaceutical Biotechnology Occupational Allergy in Healthcare Workers
Recent Patents on Inflammation & Allergy Drug Discovery Specific Aspects of Drug Hypersensitivity in Children
Current Pharmaceutical Design The Effect of SEX/Gender on Cardiovascular Pharmacology
Current Pharmaceutical Design Allergic and Pseudoallergic Reactions Induced by Glucocorticoids: A Review
Current Pharmaceutical Design Emerging Biologics in the Treatment of Inflammatory Bowel Disease: What is Around the Corner?
Current Drug Targets Skin Allergy to Azole Antifungal Agents for Systemic Use: A Review of the Literature
Recent Patents on Inflammation & Allergy Drug Discovery Nitric Oxide: State of the Art in Drug Design
Current Medicinal Chemistry The Indian Pediatric HIV Epidemic: A Systematic Review
Current HIV Research Editorial [Hot Topic: An Update on the Diagnosis of Allergic and Non-Allergic Drug Hypersensitivity (Executive Editors: M.T. Ventura and A. Romano) ]
Current Pharmaceutical Design