Genetic basis of hypersensitivity reactions to nonsteroidal anti-inflammatory drugs

Gómez, Francisca; Perkins, James R.; García‐Martín, Elena; Cantó, Gabriela; Cornejo-García, José Antonio

doi:10.1097/aci.0000000000000178

Cited by 15 publications

(15 citation statements)

References 105 publications

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“…Genetic variants in the enzymes involved in the metabolism of NSAIDs can also have a role in some types of NSAID-induced DHRs [98]. Additional information concerning the genetics of hypersensitivity to NSAIDs has recently been published [99].…”

Section: Cross-intolerance To Nsaidsmentioning

confidence: 99%

The Genetics of Drug Hypersensitivity Reactions

Cornejo-García

Jurado‐Escobar

Doña

et al. 2016

J Investig Allergol Clin Immunol

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Drug hypersensitivity reactions (DHRs) are a major problem for healthcare systems, regulatory agencies, and the pharmaceutical industry. DHRs are induced by various mechanisms and encompass a heterogeneous set of potentially life-threatening clinical entities. In addition to environmental effects, individual factors play a key role in this intricate puzzle. However, despite commendable efforts in recent years to identify individual predisposing factors, our knowledge of the genetic basis of these reactions remains incomplete. In this manuscript, we summarize current research on the genetics of DHRs, focusing on specific immune-mediated reactions (immediate and nonimmediate) and on pharmacologically mediated reactions (cross-intolerance to nonsteroidal anti-inflammatory drugs). We also provide some thoughts on potential technological approaches that would help us to decipher the molecular mechanisms underlying DHRs. We believe this manuscript will be of interest not only for allergists and basic researchers in the field, but also for clinicians from various areas of expertise who manage these reactions in their clinical practice. Key words: Drug hypersensitivity. Immediate and nonimmediate reactions. Cross-intolerance. Single-nucleotide polymorphisms. Genome-wide association study. ResumenLas reacciones de hipersensibilidad a fármacos (RHFs) son un problema preocupante para los sistemas de salud, las agencias reguladoras y la industria. Además de la diversidad de mecanismos implicados, las RHFs incluyen un conjunto heterogéneo de entidades clínicas que pueden amenazar la vida del paciente. A esta complejidad se añade el hecho de que, además de factores ambientales, en ellas participan factores individuales. A pesar del considerable esfuerzo desarrollado en los últimos años en la identificación de los factores individuales que predisponen a la aparición de estas reacciones, nuestro conocimiento sobre la base genética de las RHFs es todavía limitado. En esta revisión se presentan los datos disponibles sobre la genética de las RHFs, tomando como modelo las reacciones mediadas por mecanismos inmunológicos específicos (anticuerpos IgE y células T, reacciones inmediatas y no inmediatas) así como las mediadas por mecanismos farmacológicos (intolerancia cruzada a anti-inflamatorios no esteroideos). También se destacan las aproximaciones tecnológicas que pueden proporcionar información fundamental sobre los mecanismos moleculares que subyacen en estas reacciones. Creemos que este manuscrito será útil no solo para alergólogos e investigadores básicos en éste área, sino también para otros profesionales de la medicina que pueden encontrarse con este tipo de reacciones en su práctica clínica. Palabras clave: Hipersensibilidad a fármacos. Reacciones inmediatas y no inmediatas. Intolerancia cruzada. Polimorfismos de un único nucleótido. Estudios de asociación de genoma completo.

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Section: Cross-intolerance To Nsaidsmentioning

confidence: 99%

The Genetics of Drug Hypersensitivity Reactions

Cornejo-García

Jurado‐Escobar

Doña

et al. 2016

J Investig Allergol Clin Immunol

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“…They have mainly been performed in populations with Asian ancestry and include a limited number of patients, generally without a second population for replication [11,75,76].…”

Section: Nonallergic Reactions To Drugs: Hypersensitivity To Nsaidsmentioning

confidence: 99%

“…Most genetic association studies have followed the gene candidate approach, focusing on NERD [75,76], even though NIUA is the clinical entity most frequently induced by drug hypersensitivity [5]. They have mainly been performed in populations with Asian ancestry and include a limited number of patients, generally without a second population for replication [11,75,76].…”

Section: Nonallergic Reactions To Drugs: Hypersensitivity To Nsaidsmentioning

confidence: 99%

Update on the Genetic Basis of Drug Hypersensitivity Reactions

Jurado‐Escobar¹,

Perkins²,

García‐Martín³

et al. 2017

J Investig Allergol Clin Immunol

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Drug hypersensitivity reactions (DHRs) are unpredictable, complex responses to medicines in predisposed individuals. They represent a major health problem owing to the number of patients affected and the severity of the clinical conditions they can induce. In addition to environmental factors, the underlying mechanisms of DHRs are also influenced by genetic factors, although considerable gaps remain in our knowledge. Therefore, further study of the genetics of DHRs is necessary to shed light on their underlying mechanisms. In this manuscript, we provide an update on the genetic basis of the most frequent types of DHRs, including those mediated by immunological and nonimmunological mechanisms. For the first group, we will focus on immediate reactions to β-lactam antibiotics, which are associated mainly with the IgE pathway (IL13, IL4R, LGALS3, and NOD2) and antigen presentation (HLA-DRA), and nonimmediate reactions to allopurinol, anticonvulsants, antibiotics, and antiretrovirals, which are often associated with polymorphisms in the HLA system. For the second group, we will focus on nonsteroidal anti-inflammatory drugs, which are mostly associated with genetic variants in enzymes and receptors from the arachidonic acid pathway (eg, ALOX5, ALOX5AP, PTGDR, and CYSLTR1). The information provided here will be of interest for medical practitioners from a range of disciplines who come across these reactions in their clinical practice, as well as for allergologists. Key words: Drug hypersensitivity. Immunologically-mediated reactions. Cross-hypersensitivity. Single-nucleotide polymorphisms. Genomewide association study. ResumenLas reacciones de hipersensibilidad a fármacos (RHFs) son respuestas no predecibles que se producen en algunos sujetos y que representan un serio problema de salud pública debido al número de pacientes implicados y a su potencial gravedad. Además de factores ambientales, en estas reacciones también participan factores genéticos, cuya influencia está, en la mayoría de los casos, aún por dilucidar. En este manuscrito describiremos la información disponible sobre la base genética de los tipos más frecuentes de RHFs, tanto de las mediadas inmunológicamente como de aquellas en las que no se requiere reconocimiento antigénico. En el primer grupo nos ocuparemos de las reacciones inmediatas a antibióticos β-lactámicos, que han sido asociadas con variantes relacionadas con la IgE (IL13, IL4R, LGALS3 y NOD2) y la presentación antigénica (HLA-DRA), y de las reacciones no inmediatas a diferentes grupos de medicamentos (alopurinol, anticonvulsivos, antibióticos y antiretrovirales), relacionadas fundamentalmente con polimorfismos en el sistema HLA. En el segundo grupo nos centraremos en las reacciones inducidas por antiinflamatorios no esteroideos (AINE), que han sido asociadas básicamente con variantes en enzimas y receptores de la vía del ácido araquidónico (ALOX5, ALOX5AP, PTGDR y CYSLTR1, entre otros). Esta revisión puede ser de interés no sólo para alergólogos, sino para los profesionales de otras ...

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“…Unlike BCC, which has a low metastatic dissemination of less than 0.1%, SCC is known to be more aggressive, and the incidence of SCC metastasis, which normally arises after one to two years of diagnosis, is reported to be between 5 and 20 percent (Smoller, 2006). SCC, like every other skin cancer, is common in Caucasians (Gomez et al, 2015;Wei et al, 2015). In the USA, people of Irish or Scottish ancestry have the highest prevalence (Brantsch et al, 2008;Schwarz, 2005).…”

Section: General Introductionmentioning

confidence: 99%