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

被引：6

作者：

Perez-Garcia, Javier ^{[1
]}

Espuela-Ortiz, Antonio ^{[1
]}

Hernandez-Perez, Jose M. ^{[2
,3
]}

Gonzalez-Perez, Ruperto ^{[4
]}

Poza-Guedes, Paloma ^{[4
]}

Martin-Gonzalez, Elena ^{[1
]}

Eng, Celeste ^{[5
]}

Sardon-Prado, Olaia ^{[6
,7
]}

Mederos-Luis, Elena ^{[8
]}

Corcuera-Elosegui, Paula ^{[6
]}

Sanchez-Machin, Inmaculada ^{[8
]}

Korta-Murua, Javier

Villar, Jesus ^{[9
,10
,11
]}

Burchard, Esteban G. ^{[5
,12
]}

Lorenzo-Diaz, Fabian ^{[1
,13
,15
]}

Pino-Yanes, Maria ^{[1
,9
,14
,15
]}

机构：

[1] Univ La Laguna ULL, Dept Biochem Microbiol Cell Biol & Genet, Genom & Hlth Grp, San Cristobal la Laguna, Spain

[2] Hosp Univ NS De Candelaria, Pulm Med Sect, San Cristobal la Laguna, Tenerife, Spain

[3] Hosp Univ La Palma, Pulm Med Sect, La Palma, Spain

[4] Hosp Univ Canarias, Allergy Dept, Severe Asthma Unit, La Palma, Tenerife, Spain

[5] Univ Calif San Francisco UCSF, Dept Med, San Francisco, CA USA

[6] Hosp Univ Donostia, Div Pediat Resp Med, San Sebastian, Spain

[7] Univ Basque Country, UPV EHU, Dept Pediat, San Sebastian, Spain

[8] Hosp Univ Canarias, Allergy Dept, San Cristobal la Laguna, Tenerife, Spain

[9] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain

[10] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netwo, Res Unit, Las Palmas Gran Canaria, Spain

[11] St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada

[12] Univ Calif San Francisco UCSF, Dept Bioengn & Therapeut Sci, San Francisco, CA USA

[13] Univ La Laguna ULL, Inst Univ Enfermedades Trop & Salud Publ Canarias, San Cristobal la Laguna, Spain

[14] Univ La Laguna ULL, Inst Tecnol Biomed, San Cristobal la Laguna, Tenerife, Spain

[15] Univ La Laguna, Dept Biochem Microbiol Cell Biol & Genet, Genom & Hlth Grp, Apartado 456, Santa Cruz De Tenerife 38200, Spain

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2023年 / 152卷 / 03期

关键词：

Gene -set enrichment analyses; therapeutic drug; GENOME-WIDE ASSOCIATION; GALA II; OBESITY; EXPRESSION;

D O I：

10.1016/j.jaci.2023.05.021

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: 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. Objective: We sought to identify genes and biological pathways regulating airway-microbiome traits involved in asthma Methods: Saliva, nasal, and pharyngeal samples from 257 European patients with asthma were analyzed. The association microbiome genome-wide association studies. Variants with 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. Results: Genes associated with exacerbation-related airwaymicrobiome traits were enriched in asthma comorbidities were likely regulated by trichostatin A and the nuclear factorKB, the glucocorticosteroid receptor, and CCAAT/enhancerStreptococcus, Tannerella, and Campylobacter in the upper Conclusions: Genes associated with asthma exacerbation-

引用

页码：799 / +

页数：14

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