TSLP disease-associated genetic variants combined with airway TSLP expression influence asthma risk - 05/01/22
Abstract |
Background |
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.
Objectives |
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.
Methods |
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.
Results |
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 tertile) had asthma compared with 40% of subjects without risk genotypes and with low TSLP expression (bottom tertile) (P = .024). No association between circulating TSLP and asthma was observed.
Conclusions |
Collectively, these data suggest childhood asthma is modified by the combined effects of TSLP genotype and TSLP expression in the nasal epithelium. The increased asthma risk likely manifests when genetic variation enables expression quantitative trait loci in the TSLP locus to elevate TSLP. It is important to consider both biomarkers when factoring asthma risk.
Le texte complet de cet article est disponible en PDF.Key words : TSLP, asthma, genotype, gene, biomarker, gene expression, mRNA
Abbreviations used : AD, eQTL, FAIRE, GWAS, LD, lfTSLP, MAF, NEC, OR, sfTSLP, SNP, TSLP
Plan
| Supported by National Institute of Allergy and Infectious Diseases grant R01AI127392 (to G.K.K.H., L.B.M., J.M.B., L.J.M., R.K.) and U19AI1070235 (to G.K.K.H., J.M.B., L.J.M.). |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 149 - N° 1
P. 79-88 - janvier 2022 Retour au numéro
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