Association Study of Functional Polymorphisms in Genes Involved in Histamine Homeostasis and Multiple NSAID–Triggered Urticaria and/or Angioedema and Anaphylaxis in Patients without Pre-Existing Chronic Urticaria (MNSAID-UA)

Abstract

M O N D A Y 599 Association of Thymic Stromal Lymphopoietin Genetic Variants in Urticaria/Angioedema Induced by Multiple Nsaids Maria del Carmen Plaza-Ser on, Bsc, Pedro Ayuso Parejo, PhD, Natalia Blanca-L opez, MD, PhD, Inmaculada Do~na, MD, PhD, Mar ia Jos e Torres, MD, PhD, Javier Fern andez, Jose Julio Laguna, Veronique Goidenau, Luisa Galindo, RN, Rocio Herrera, NR, Gabriela Canto, MD, PhD, Miguel Blanca, MD, PhD, Jose Antonio Cornejo-Garc ia; Allergy Service, Infanta Leonor Hospital, Malaga, Spain, Allergy Service, Infanta Leonor Hospital, Madrid, Spain, IMABIS Foundation, Malaga, Spain, Imabis Foundation, Alicante Hospital, Hospital De La Cruz Roja, Madrid, Spain, Carlos Haya Hospital, Malaga, Spain, Alergy Service Carlos Haya Hospital, Malaga, Spain, Allergy Service, Infanta Leonor Hospital, Allergy Service, Carlos Haya Hospital, M alaga, Spain. RATIONALE: NSAIDs are the most frequent agents involved in hypersensitivity reactions to drugs (HDR), being urticaria/angioedema (MNSAID-UA) the most relevant clinical entity. A significant proportion of MNSAID-UA patients show a high prevalence of atopic status. The thymic stromal lymphopoietin (TSLP) is involved in the inflammatory skin response mediated by mast cells. These are key players in MNSAID-UA. An association of SNPs in the TSLP gene and its receptor (IL7Ra and TSLPR) has been reported in other inflammatory diseases. In this work, we analyzed the potential association between SNPs in TSLP, IL7Ra and TSLPR, and MNSAID-UA. METHODS: A total of 394 patients with MNSAID-UA and 257 controls who tolerated NSAIDs were included. This is a part of a study carried out by the Spanish National Network for Allergy (RIRAAF). A total of 6 tSNPs inTSLP, 6 tSNPs in IL7Ra and 3 tSNPs inTSLPRwere genotyped by using TaqMan O probes. Statistical analysis was done using SPSS 11.5 program and Haploview. RESULTS: Statistically significant differences were found only for SNPs rs1545169 and rs764917 in TSLP gene (p< 0.0001, and p< 0.014; respectively). After atopic status adjustment, these differences were not observed. CONCLUSIONS: Although genetic variants in TSLP and related genes appear not be associated with MNSAID-UA, these SNPs could play a role in atopy. Further studies are needed to unveil the interaction between these two entities.