Single Nucleotide Polymorphisms in Thymic Stromal Lymphopoietin Gene are not Associated with Aspirin-Exacerbated Respiratory Disease Susceptibility - A Pilot Study in a Japanese Population

Abstract

Background: Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine, implicated in the development and progression of allergic diseases. Several studies indicated polymorphisms in TSLP gene were associated asthma, and two single nucleotides polymorphisms (SNPs) in TSLP (rs1837253 and rs2289276) were shown to be associated with asthma in a sex-specific fashion. However, there has been no report that investigated TSLP gene polymorphisms in patients with aspirin-exacerbated respiratory disease (AERD). Methods: DNA specimens were obtained from the following three groups: 105 patients with AERD, 270 patients with aspirin-tolerant asthma (ATA) and 90 normal controls. The target DNA sequence of the TSLP gene was amplified using a set of primers. Allelic discrimination assay for the two SNPs in TSLP gene (rs1837253 and rs2289276) was carried out. All patients were Japanese, and they were in a stable condition. Results: The frequency of the T minor allele of TSLP-5717C>T in patients with AERD and those with ATA was significantly higher than that in normal controls. There were no significant difference of the T minor allele frequency of TSLP-82C>T among the three groups. Analysis of genotype frequencies of the CT/TT genotype group and CC genotype both in TSLP-5717C>T and in TSLP-82C>T showed no differences between AERD and ATA patients. In addition, subgroup analysis of the genotype frequencies with gender did not differ between AERD and ATA patients. Conclusion: This is the first pilot study to investigate TSLP gene polymorphisms in AERD, which didn't find an association between the TSLP gene polymorphisms and AERD susceptibility in a Japanese population, suggesting polymorphisms in TSLP gene may contribute to asthma, but not to aspirin hypersensitivity.

Genetic Variants of Thymic Stromal Lymphopoietin in Nonsteroidal Anti-Inflammatory Drug-Induced Urticaria/Angioedema

“…TSLP polymorphisms have been studied in the context of respiratory [12,13,14,35,36,37] and cutaneous diseases [10,11], including NERD [9]. However, in this study only two imputed SNPs showed a nominal genetic association (rs1816678 and rs764917) with NIUA, suggesting a potential role of TSLP in NIUA, although this must be confirmed.…”

“…Several candidate gene association studies have assessed the importance of TSLP in NSAID-exacerbated respiratory disease (NERD) [9], atopic dermatitis [10] and eczema [11], as well as other allergy-related pathologies. In addition, genome-wide association studies have found single nucleotide polymorphism (SNPs) in TSLP to be associated with asthma [12], allergic rhinitis [13,14] and eosinophilic esophagitis in children [15].…”

Interleukin (IL)-13, IL-17A, and Mast Cell Chymase Gene Polymorphisms in Bronchial Asthma and Chronic Obstructive Pulmonary Disease – A Pilot Study in a Japanese Population

“…The target of DNA sequence of the CMA1 -1903G>A was amplified using a set of primers (forward: 5'-GAGCAGATAGTGCAGTC-CTCGTTTC-3' , reverse: 5'-CTCCACAGCATCAAGATTCA-GATCC-3'). Allelic discrimination assay for SNPs relating to the expressions of IL-13 -1111C>T, IL-13 Arg110Gln, IL-17A -737C>T and CMA1 -1903G>A (rs1800925, rs20541, rs8193036 and rs1800875, respectively) was carried out by a SNPs detective system as described [41][42][43][44]. All subjects and investigators remained unaware of the genotype until the final analysis.…”