PID1 is associated to a respiratory endotype related to occupational exposures to irritants.
Asthma
Endotypes
Gene association study
Irritants
Occupational exposure
Oxidative stress
Journal
Free radical biology & medicine
ISSN: 1873-4596
Titre abrégé: Free Radic Biol Med
Pays: United States
ID NLM: 8709159
Informations de publication
Date de publication:
20 08 2021
20 08 2021
Historique:
received:
22
03
2021
revised:
26
05
2021
accepted:
27
05
2021
pubmed:
5
6
2021
medline:
27
8
2021
entrez:
4
6
2021
Statut:
ppublish
Résumé
Studying associations between genes and asthma endotypes and interactions with environment could help to identify new susceptibility genes. We used a previously identified asthma endotype characterized by adult-onset asthma, poor lung function, and high level of Fluorescent oxidation products, a marker of damages due to oxidative stress. This endotype was associated with high occupational exposure to irritants. We aimed to investigate the associations between genes related to oxidative stress and this endotype, and if the associations differed according to irritants exposure. We conducted association analyses between the asthma endotype and genetic variants (4715 SNPs) located in 422 genes involved in the "response to oxidative stress" in adults from the Epidemiological study on the Genetic and Environment of Asthma. Analyses using logistic regression were conducted first in all participants, and then separately among high vs. non-exposed participants to assess whether association differs according to irritants exposure. An association was found between the SNP rs1419958 located in PID1 gene and the endotype (P = 2.2E-05), reaching significance level after correction for multiple testing. This association was even more significant in non-exposed participants (P = 1.06E-06) while there was no association in participants with high exposure to occupational irritants. This study showed a significant association between an asthma endotype and PID1, a promising candidate gene, the association being different according to the exposure to irritants. These results highlight the interest of studying asthma endotypes in association with genes from candidate pathways and their link with occupational irritants to decipher asthma etiology.
Sections du résumé
BACKGROUND
Studying associations between genes and asthma endotypes and interactions with environment could help to identify new susceptibility genes. We used a previously identified asthma endotype characterized by adult-onset asthma, poor lung function, and high level of Fluorescent oxidation products, a marker of damages due to oxidative stress. This endotype was associated with high occupational exposure to irritants. We aimed to investigate the associations between genes related to oxidative stress and this endotype, and if the associations differed according to irritants exposure.
METHODS
We conducted association analyses between the asthma endotype and genetic variants (4715 SNPs) located in 422 genes involved in the "response to oxidative stress" in adults from the Epidemiological study on the Genetic and Environment of Asthma. Analyses using logistic regression were conducted first in all participants, and then separately among high vs. non-exposed participants to assess whether association differs according to irritants exposure.
RESULTS
An association was found between the SNP rs1419958 located in PID1 gene and the endotype (P = 2.2E-05), reaching significance level after correction for multiple testing. This association was even more significant in non-exposed participants (P = 1.06E-06) while there was no association in participants with high exposure to occupational irritants.
CONCLUSION
This study showed a significant association between an asthma endotype and PID1, a promising candidate gene, the association being different according to the exposure to irritants. These results highlight the interest of studying asthma endotypes in association with genes from candidate pathways and their link with occupational irritants to decipher asthma etiology.
Identifiants
pubmed: 34087431
pii: S0891-5849(21)00349-X
doi: 10.1016/j.freeradbiomed.2021.05.038
pii:
doi:
Substances chimiques
Carrier Proteins
0
Irritants
0
PID1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
503-507Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.