Functional variability of the adenosine A3 receptor (<i>ADORA3</i>) gene polymorphism in aspirin-induced urticaria

Kim, S.-H.; Nam, Eon Jeong; Kim, Y.-K.; Ye, Y.-M.; Park, Hae‐Sim

doi:10.1111/j.1365-2133.2010.09983.x

Cited by 31 publications

(25 citation statements)

References 34 publications

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“…Finally, further associations have been found with the adenosine receptor A3 gene (-1050G>T and -564C>T) [117], IL4 (-589T>C) [112,118], IL10 (-1082 G>A) [112], CTLA (49A>G) [112], nitric oxide synthase 2 [119], and the HLA system [120][121][122].…”

Section: Other Variants Outside Eicosanoid Biosynthesismentioning

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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Section: Other Variants Outside Eicosanoid Biosynthesismentioning

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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“…Nevertheless, the missense polymorphism rs10156191 (Thr16Met) in diamine oxidase, which causes impaired metabolism of circulating histamine, was associated with NIUA, NERD, and a mixed reaction pattern [91]. Other genetic associations in NSAID-induced DHRs have been found with polymorphisms in the adenosine receptor A3 gene (ADORA3) (-1050G>T and -564C>T), IL4 (-589T>C) [90], IL13 (-1111C>T), and HLA [92][93][94][95][96]. We analyzed 9 SNPs in 5 genes involved in mast cell activation in NIUA and found statistically significant differences when patients were stratified according to clinical symptoms [97].…”

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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“…3 Leukotriene overproduction may be one of the mechanisms responsible for AIU, 1,4 which is supported by genetic studies showing significant association of leukotriene C4 synthase (LTC4S) 5,6 and 5-lipoxygenase (ALOX5). 7 In addition, previous genetic association studies have reported that the IgE high affinity receptor (FCER1A), 8 histamine N-methyltransferase (HNMT) 9 and adenosine A3 receptor (ADORA3) 10 genes are genetic determinants of AIU, which indicates that genetic variation associated with increased histamine release and ⁄or augmented mast cell signalling, leading to the release of proinflammatory mediators, can contribute to the development of AIU.…”

Section: Discussionmentioning

confidence: 99%

“…This is supported by our previous research, which suggested that neutrophil activation may be involved in the pathogenesis of AIAU. 2,10,11 In this study, better to understand the role of IL-18 in the development of AIAU, we examined the effect of the high transcript haplotype, ht1 [CG], on neutrophil chemotaxis in peripheral blood neutrophils from patients with AIU. We found increased neutrophil chemotaxis in subjects exhibiting the high transcript haplotype ht1 [CG], and decreased neutrophil chemotaxis in those with the low transcript haplotype ht2 [AG].…”

Section: Discussionmentioning

confidence: 99%

A functional promoter polymorphism of the human IL18 gene is associated with aspirin-induced urticaria

et al. 2011

British Journal of Dermatology

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SummaryBackground Urticaria is the commonest cutaneous reaction caused by aspirin or other nonsteroidal anti-inflammatory drugs. The pathogenesis of aspirin-induced urticaria (AIU) is not fully understood, but appears to involve mast cell activation and neutrophil infiltration. Objectives To investigate the genetic contribution of interleukin (IL)-18, which can amplify acute inflammation by promoting mast cell activation, neutrophil migration and cytokine production, to the pathogenesis of AIU. Methods A case-control association study was performed using 275 patients with AIU and 196 normal healthy controls in a Korean population. Two promoter polymorphisms of the IL18 gene ()607A ⁄C and )137G ⁄C) were genotyped using the primer extension method. The functional effect of the IL18 gene promoter polymorphism was investigated through in vitro studies including a luciferase reporter assay and electrophoretic mobility shift assays (EMSAs) and ex vivo studies involving neutrophil chemotaxis assays. Results A significant association was detected between both AIU in general and the aspirin-intolerant acute urticaria (AIAU) phenotype and the IL18 promoter polymorphism )607A ⁄C. Patients with AIAU showed higher frequencies of the C )607 G )137 haplotype, ht1 [CG], compared with controls (P = 0AE02). Moreover, ht1 [CG] showed a high transcript haplotype by the luciferase activity assay, and EMSAs identified a )607C allele-specific DNA-binding protein as CREB2. Neutrophil chemotactic activity was highest in subjects with AIU exhibiting the high transcript haplotype, ht1 [CG] (P = 0AE019). Conclusions The high transcript haplotype ht1 [CG] of the IL18 gene may contribute to the development of acute cutaneous inflammation sensitive to aspirin, leading to the clinical presentation of AIAU.

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Functional variability of the adenosine A3 receptor (ADORA3) gene polymorphism in aspirin-induced urticaria

Cited by 31 publications

References 34 publications

Update on the Genetic Basis of Drug Hypersensitivity Reactions

Update on the Genetic Basis of Drug Hypersensitivity Reactions

The Genetics of Drug Hypersensitivity Reactions

A functional promoter polymorphism of the human IL18 gene is associated with aspirin-induced urticaria

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