Update on the Genetic Basis of Drug Hypersensitivity Reactions

Abstract

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 ...

Self-Reported Drug Hypersensitivity Amongst Late Adolescents in Mexico: A Population Based Study

“…Our data are consistent with previous reports [2,5,6]. It is likely that patients with previous adverse reactions to medications are quicker to identify them in their own family.…”

“…Lastly, we found a significant association between a personal history of asthma and prevalence of DHR. Multiple studies conducted around the world, including Mexico, support the hypothesis that allergic conditions are a risk factor for drug hypersensitivity [1,3,5,6].…”

“…For many years, antibiotics have been the main culprits, followed by nonsteroidal anti-inflammatory drugs (NSAIDs). Risk factors for DHR include female sex, age, presence of allergic disease, ethnicity, and genetics [3][4][5][6]. Given the lack of previous studies aimed at defining the magnitude of DHR in Latin America, our main objective was to identify factors associated with the prevalence of DHR in late adolescents.…”

Nonsteroidal anti-inflammatory drug hypersensitivity in the Asia-Pacific

“…There are several genome-wide association and case-control studies on NSAID HSR which originate from this region, in particular from Korea and Japan [ 10 11 ]. Genetic polymorphisms have been described mainly for NERD, with limited studies on NECD/ NIUA.…”

Recurrent Drug-Induced Liver Injury With Cetirizine and Amoxicillin–Clavulanate Potassium

“…Susceptibility to DILI is believed to result from interplay of multiple factors, including the structure of the drug, the patient's genetic background, the influence of underlying diseases, and associated medications [5]. Nevertheless, a genetic basis for DILI has not been determined [6].…”