TSLP disease-associated genetic variants combined with airway TSLP expression influence asthma risk.
Abstract
Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine important in initiation of allergic inflammation. Single nucleotide polymorphisms (SNPs) in TSLP are associated with asthma, yet studies have shown inconsistent associations between circulating TSLP and asthma. Studies that integrate the combined effects of TSLP genotype, TSLP mRNA, circulating TSLP levels, and asthma outcome are lacking. This study sought to recruit a novel cohort based on asthma-relevant TSLP SNPs and determine their impact on TSLP mRNA expression and TSLP circulating protein levels, and their individual and combined effects on asthma. This study developed an algorithm to prioritize TSLP SNPs and recruited 51 carriers and noncarriers based on TSLP genotypes. TSLP mRNA was quantified in nasal epithelial cells and circulating TSLP levels in plasma. This study determined the associations of defined TSLP risk genotypes and/or TSLP mRNA and protein levels with asthma. TSLP mRNA expression, but not circulating TSLP, was significantly increased in people who are asthmatic compared with in people who are nonasthmatic (P = .007; odds ratio, 1.44). Notably, 90% of children with the defined TSLP risk genotypes and high nasal TSLP mRNA expression (top ...Continue Reading
References
Functional analysis of the thymic stromal lymphopoietin variants in human bronchial epithelial cells
A thymic stromal lymphopoietin gene variant is associated with asthma and airway hyperresponsiveness
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