Association of TRPM3 Polymorphism (rs10780946) and Aspirin-Exacerbated Respiratory Disease (AERD).

INTRODUCTION: Aspirin-exacerbated respiratory disease (AERD) refers to the combination of asthma rhinosinusitis and poliposis; ingestion of aspirin or other non-steroid anti-inflammatory drugs exacerbate asthma-like symptoms. The pathogenesis of AERD is unknown, and genetic and environmental factors contribute to the disease. Our objective is identifying polymorphisms associated with susceptibility in a Mexican mestizo population. METHODS: Primarily we performed custom Illumina goldengate array-based genotyping of 1512 SNPs, carefully selected from a variety of acute/chronic inflammatory lung conditions previously reported. Four SNPs in TRPM3 gene showed the lowest p-values (rs10780946, rs7025694, rs1889915, and rs7047645). We further selected rs10780946 and rs7025694 for validation using Taqman genotyping (n = 743; 288 AERD, 272 ATA, and 183 HC). RESULTS: rs10780946 showed association when compared between AERD and ATA groups under co-dominant (p = 0.006), dominant (p = 0.002), overdominant (p = 0.01), and log-additive (p = 0.03) genetic models. AERD showed increased heterozygous TC (rs10780946-rs7025694) haplotype compared to ATA and HC (p < 0.05). We could not confirm any association between rs7025694 and AERD. CONCLUSION: rs10780946 TRPM3 polymorphism is associated with AERD susceptibility.

Intolerancia a la aspirina en pacientes con poliposis nasal y asma bronquial / Aspirin intolerante in patients with nasal polyps and asthma

La tríada de la aspirina, caracterizada por intolerancia a la aspirina, asma bronquial y poliposis nasal, fue descrita inicialmente por Widal en 1922. La prevalencia de intolerancia a la aspirina en la población general es de aproximadamente 6 por ciento, pero estudios han revelado que hasta 78 por ciento de los pacientes con poliposis nasal padecen la triada. La presentación clínica consiste en un patrón característico evolutivo de la aparición de los síntomas, presentándose en primer lugar rinitis, luego poliposis nasal, asma bronquial y finalmente IA. Si bien es sabido que esta patología corresponde a una pseudoalergia, donde ocurre una degranulación inespecífica de los mastocitos, los mecanismos fisiopatológicos que gatillan esta degranulación no están totalmente dilucidados, siendo la hipótesis más aceptada actualmente aquella que guarda relación con las modificaciones en el metabolismo del ácido araquidónico causadas por la aspirina. Actualmente no existen exámenes de laboratorio para la confirmación diagnóstica de intolerancia a la aspirina, por lo que frente a la sospecha clínica de esta patología debe someterse al paciente a pruebas de provocación para hacer el diagnóstico certero de esta enfermedad, siendo la más utilizada la prueba de provocación con aspirina oral.

The aspirin triad, characterized by aspirin intolerance, bronchial asthma and nasal polyposis was first described by Widal in 1922. Prevalence of aspirin intolerance in the general population is near 6 percent, but studies have shown that 78 percent of the patients with nasal polyps suffer from the triad. Clinical presentation consists of a characteristic evolutive pattern, with rhinitis appearing first, then nasal polyps, bronchial asthma and finally aspirin intolerance. Even though it is well known that this pathology corresponds to pseudoallergy where unspecific mast cell degranulation occurs, the physiopathologic mechanisms that trigger this degranulation are not completely understood. The most accepted hypothesis involves aspirin-induced modifications in the metabolism of arachidonic acid. Currently there are no in vitro tests available for aspirin intolerance diagnosis, so if this pathology is suspected, a provocation test with aspirin is necessary to confirm the diagnosis, oral provocation test being the most frequently used in clinical practice.