Long-Term PM2.5 Exposure and Upregulation of CLCA1 Expression in Nasal Epithelium from Youth with Asthma.
Ann Am Thorac Soc
; 2024 Jul 10.
Article
en En
| MEDLINE
| ID: mdl-38986136
ABSTRACT
BACKGROUND:
Little is known about long-term PM2.5 exposure and airway epithelial gene expression.OBJECTIVE:
To test for association between long-term PM2.5 exposure and nasal epithelial gene expression in youth with asthma.METHODS:
Transcriptome-wide association study (TWAS) of long-term PM2.5 in nasal epithelium from youth aged 6-20 years in the 1) Epigenetic Variation and Childhood Asthma in Puerto Ricans study (EVA-PR, n=182); 2) Vitamin D Kids Asthma Study (VDKA, n=58); and 3) Stress and Treatment Response in Puerto Rican and African American Children with Asthma study (STAR, n=81). Satellite hybrid models were used to estimate PM2.5 exposure in the prior year at each participant's residence. Multivariable negative binomial regression was used for each TWAS, adjusting for age, sex, and other covariates. A meta-analysis of all TWAS results was then conducted using an inverse variance-weighted average approach.RESULTS:
Most participants (~95%) in the meta-analysis of TWAS for PM2.5 exposure identified as Puerto Rican or Black. Long-term PM2.5 was associated with 1) upregulated expression of CLCA1 (calcium-activated chloride channel regulator 1, false discovery rate-adjusted P [FDR-P]=0.008), SYCP2 (synaptonemal complex protein 2, FDR-P=0.01), and CYP2A6 (cytochrome p450 family 2 subfamily A member 6, FDR-P=0.02), and 2) downregulated expression of EDAR (ectodysplasin A receptor, FDR-P=0.01). In a meta-analysis, CLCA1 upregulation was associated with ≥1 positive allergen-specific IgE (FDR-P <0.001) and increased blood eosinophils (FDR-P <0.001) and total IgE (FDR-P <0.001).CONCLUSIONS:
In a meta-analysis of TWASs in predominantly Puerto Rican and Black youth with asthma, long-term PM2.5 exposure was associated with upregulated airway epithelial CLCA1 expression, in turn linked to biomarkers of T2-high immunity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Ann Am Thorac Soc
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos