Genetic variants of the arachidonic acid pathway in non‐steroidal anti‐inflammatory drug‐induced acute urticaria

Cornejo-García, José Antonio; Jagemann, L.R.; Blanca‐López, Natalia; Doña, Inmaculada; Flores, Carlos; Guéant-Rodríguez, Rosa-María; Torres, Marı́a José; Fernández, J.; Laguna, José Julio; Rosado, A.; Agúndez, José A. G.; García‐Martín, Elena; Cantó, Gabriela; Guéant, Jean‐Louis; Blanca, Miguel

doi:10.1111/j.1365-2222.2012.04078.x

Cited by 54 publications

(86 citation statements)

References 65 publications

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“…We found that the rs1132340 SNP in ALOX5 activating protein was associated with NIUA [88], an association that was not found in NERD patients in Korea [84]. In another Spanish study, no association was found with the ALOX5 rs4948672 SNP in NIUA patients [91].…”

Section: Enzyme and Receptor Genes From The Arachidonic Acid Metabolicontrasting

confidence: 50%

“…In another Spanish study, no association was found with the ALOX5 rs4948672 SNP in NIUA patients [91]. As for ALOX15, we found a statistically significant association between the promoter variant -272C>A (rs7220870) and NIUA in 2 independent populations from Spain [88], although this association was not found in Korean patients [92]. We recently reported an association between the rs3892408 ALOX15 genetic variant and Spanish NERD patients [89].…”

Section: Enzyme and Receptor Genes From The Arachidonic Acid Metabolimentioning

confidence: 54%

“…The minor allele frequency (MAF) of this SNP was also found to be higher for NECD patients in Poland [86], but not for patients with NSAID-induced angioedema in Spain [87]. Furthermore, in a Spanish study including the largest number of cross-hypersensitivity patients published to date, we were unable to find an association between the rs730012 variant and NIUA [88]. The variants rs5789 and rs10306135 in prostaglandin-endoperoxide synthase 1 (COX-1 gene) were shown to be associated with NERD [89].…”

Section: Enzyme and Receptor Genes From The Arachidonic Acid Metabolimentioning

confidence: 62%

“…The MAF of PTGER4 -1254G>A was recently found to be higher in NECD patients than in healthy individuals [96]. Finally, the rs8004654 polymorphism in PGDR was shown to be significantly associated with NIUA in 2 independent Spanish populations [88], as well as in American asthmatics [97].…”

Section: Enzyme and Receptor Genes From The Arachidonic Acid Metabolimentioning

confidence: 91%

“…Statistically significant associations have been found for prostaglandin receptor PGER1-4 and PGGIR gene polymorphisms in NERD [94,95]. We previously reported associations for 2 SNPs in PGE1R (rs3810253 and rs3810255) and 1 in PGER2 (rs1254598) [88] in NIUA, neither of which was found in Asian NERD patients [94]. The MAF of PTGER4 -1254G>A was recently found to be higher in NECD patients than in healthy individuals [96].…”

Section: Enzyme and Receptor Genes From The Arachidonic Acid Metabolimentioning

confidence: 91%

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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: Enzyme and Receptor Genes From The Arachidonic Acid Metabolicontrasting

confidence: 50%

Section: Enzyme and Receptor Genes From The Arachidonic Acid Metabolimentioning

confidence: 54%

Section: Enzyme and Receptor Genes From The Arachidonic Acid Metabolimentioning

confidence: 62%

Section: Enzyme and Receptor Genes From The Arachidonic Acid Metabolimentioning

confidence: 91%

Section: Enzyme and Receptor Genes From The Arachidonic Acid Metabolimentioning

confidence: 91%

See 3 more Smart Citations

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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Polymorphism of IL10, IL4, CTLA4, and DAO Genes in Cross‐Reactive Nonsteroidal Anti‐inflammatory Drug Hypersensitivity

Vasconcelos

Rodrigues

Albuquerque

et al. 2017

The Journal of Clinical Pharma

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Our aim was to evaluate genetic polymorphism of molecules involved in immunoregulatory/allergic processes in patients who presented with cutaneous hypersensitivity caused by chemically unrelated nonsteroidal anti-inflammatory drugs. Polymorphisms at IL10 (-1082 G>A), IL4 (-589 C>T), CTLA4 (+49A>G), and DAO (+8956 C>G) genes were studied in 55 cases and 97 controls by the polymerase chain reaction-restriction fragment length polymorphism technique. With regard to the polymorphism at IL10 -1082, higher frequencies of the AG genotype (57% vs 39%) and G allele carriers (70% vs 48%) were found among the patients, indicating a risk effect (odds ratio [OR] = 2.56 and P = .01 for AG genotype and OR = 2.52; P = .01 for AG/GG). For the CTLA4 +49 A/G single-nucleotide polymorphism (SNP), AG genotype (31.0%) (P = .02) and G carrier (54.0%) (P = .05) frequencies were found to be significantly lower in the patient group compared with the control group (51.0% and 69.0%, respectively). The SNP DAO +8956 C>G was associated with a strong protective effect, with OR values of 0.83 for CG and 0.11 for GG genotype (P = .04 for the codominant model), suggesting an allele dose effect. The combination of IL10 and DAO SNPs in a multivariate model did not alter the OR values, suggesting independent effects for both SNPs. The results are striking. In conclusion, these results suggest that polymorphisms in regulatory targets of the immune response and in DAO gene could modulate an individual's susceptibility to nonsteroidal anti-inflammatory drug hypersensitivity reactions. Further studies will be necessary to complement our results.

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