title: Association of TRPM3 Polymorphism (rs10780946) and Aspirin-Exacerbated Respiratory Disease (AERD).
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  rs10780946 TRPM3 polymorphism is associated with AERD susceptibility.
authors.affiliation: Department of Allergy and Clinical Immunolgy, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico, D. F., Mexico.|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.
authors.forename: Arun
authors.initials: A
authors.lastname: Narayanankutty
authors.affiliation: 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.|Departamento de Morfología, Facultad de Medicina Veterinaria y Zootecnia., Universidad Nacional Autónoma de México, Ciudad Universitaria #3000, Coyoacán, 04510, Mexico, D. F., Mexico.
authors.forename: Icela
authors.initials: I
authors.lastname: Palma-Lara
authors.affiliation: Department of Allergy and Clinical Immunolgy, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico, D. F., Mexico.
authors.forename: Gandhi
authors.initials: G
authors.lastname: Pavón-Romero
authors.affiliation: Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico, D. F., Mexico.
authors.forename: Gloria
authors.initials: G
authors.lastname: Pérez-Rubio
authors.affiliation: Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico, D. F., Mexico.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Camarena
authors.affiliation: 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.|Biomedicine In the Post-Genomic Era, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico, D. F., Mexico. lmteran@ier.gob.mx.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Teran
authors.affiliation: Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico, D. F., Mexico. rfalfanv@iner.gob.mx.
authors.forename: Ramcés
authors.initials: R
authors.lastname: Falfán-Valencia
mesh_terms: D000328:Adult; D000368:Aged; D055963:Asthma, Aspirin-Induced / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050053:TRPM Cation Channels / Q000235:genetics*; D055815:Young Adult
chemical_list: D050053:TRPM Cation Channels; C475667:TRPM3 protein, human
keywords: AERD; Aspirin intolerance; Association study; Ca2+ channel; TRPM3