Details

Autor(en) / Beteiligte

• Perez-Garcia, Javier
• Espuela-Ortiz, Antonio
• Hernández-Pérez, José M.
• González-Pérez, Ruperto
• Poza-Guedes, Paloma
• Martin-Gonzalez, Elena
• Eng, Celeste
• Sardón-Prado, Olaia
• Mederos-Luis, Elena
• Corcuera-Elosegui, Paula
• Sánchez-Machín, Inmaculada
• Korta-Murua, Javier
• Villar, Jesús
• Burchard, Esteban G.
• Lorenzo-Diaz, Fabian
• Pino-Yanes, Maria

Titel

Human genetics influences microbiome composition involved in asthma exacerbations despite inhaled corticosteroid treatment

Ist Teil von

• Journal of allergy and clinical immunology, 2023-09, Vol.152 (3), p.799-806.e6

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] The upper-airway microbiome is involved in asthma exacerbations despite inhaled corticosteroid (ICS) treatment. Although human genetics regulates microbiome composition, its influence on asthma-related airway bacteria remains unknown. We sought to identify genes and biological pathways regulating airway-microbiome traits involved in asthma exacerbations and ICS response. Saliva, nasal, and pharyngeal samples from 257 European patients with asthma were analyzed. The association of 6,296,951 genetic variants with exacerbation-related microbiome traits despite ICS treatment was tested through microbiome genome-wide association studies. Variants with 1 × 10−4 <P < 1 × 10−6 were examined in gene-set enrichment analyses. Significant results were sought for replication in 114 African American and 158 Latino children with and without asthma. ICS-response–associated single nucleotide polymorphisms reported in the literature were evaluated as microbiome quantitative trait loci. Multiple comparisons were adjusted by the false discovery rate. Genes associated with exacerbation-related airway-microbiome traits were enriched in asthma comorbidities development (ie, reflux esophagitis, obesity, and smoking), and were likely regulated by trichostatin A and the nuclear factor-κB, the glucocorticosteroid receptor, and CCAAT/enhancer-binding protein transcription factors (7.8 × 10−13 ≤ false discovery rate ≤ 0.022). Enrichment in smoking, trichostatin A, nuclear factor-κB, and glucocorticosteroid receptor were replicated in the saliva samples from diverse populations (4.42 × 10−9 ≤ P ≤ .008). The ICS-response–associated single nucleotide polymorphisms rs5995653 (APOBEC3B-APOBEC3C), rs6467778 (TRIM24), and rs5752429 (TPST2) were identified as microbiome quantitative trait loci of Streptococcus, Tannerella, and Campylobacter in the upper airway (0.027 ≤ false discovery rate ≤ 0.050). Genes associated with asthma exacerbation–related microbiome traits might influence asthma comorbidities. We reinforced the therapeutic interest of trichostatin A, nuclear factor-κB, the glucocorticosteroid receptor, and CCAAT/enhancer-binding protein in asthma exacerbations.