Arun Narayanankutty1,2, Icela Palma-Lara2,3, Gandhi Pavón-Romero1, Gloria Pérez-Rubio4, Ángel Camarena4, Luis M Teran5,6, Ramcés Falfán-Valencia7. 1. Department of Allergy and Clinical Immunolgy, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico, D. F., Mexico. 2. Laboratorio de Morfología Celular y Molecular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, 11340, Mexico, D. F., Mexico. 3. Departamento de Morfología, Facultad de Medicina Veterinaria y Zootecnia., Universidad Nacional Autónoma de México, Ciudad Universitaria #3000, Coyoacán, 04510, Mexico, D. F., Mexico. 4. Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico, D. F., Mexico. 5. Department of Allergy and Clinical Immunolgy, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico, D. F., Mexico. lmteran@ier.gob.mx. 6. Biomedicine In the Post-Genomic Era, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico, D. F., Mexico. lmteran@ier.gob.mx. 7. Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico, D. F., Mexico. rfalfanv@iner.gob.mx.
Abstract
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.
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:rs10780946TRPM3 polymorphism is associated with AERD susceptibility.
Entities:
Keywords:
AERD; Aspirin intolerance; Association study; Ca2+ channel; TRPM3
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