Association analyses of eQTLs of the TYRO3 gene and allergic diseases in Japanese populations.
Adolescent
Adult
Aged
Aged, 80 and over
Asian People
/ genetics
Case-Control Studies
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Hypersensitivity
/ epidemiology
Lung
/ metabolism
Male
Middle Aged
Odds Ratio
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Receptor Protein-Tyrosine Kinases
/ genetics
Young Adult
Allergic rhinitis
Asthma
Atopy
TYRO3
eQTL
Journal
Allergology international : official journal of the Japanese Society of Allergology
ISSN: 1440-1592
Titre abrégé: Allergol Int
Pays: England
ID NLM: 9616296
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
11
04
2018
revised:
07
06
2018
accepted:
07
07
2018
pubmed:
8
8
2018
medline:
2
4
2019
entrez:
8
8
2018
Statut:
ppublish
Résumé
TYRO3 is a member of the TAM (TYRO3, AXL, MERTK) receptor tyrosine kinase family and functions to limit type 2 immune responses implicated in allergic sensitization. Recent studies have shown that multiple intronic variants of TYRO3 were associated with asthma, implying that genetic variation could contribute to errant immune activation. We therefore hypothesized that expression quantitative trait loci (eQTLs) of the TYRO3 gene influence the development of allergic diseases (including asthma and allergic rhinitis) in Japanese populations. We performed a candidate gene case-control association study of 8 eQTLs of TYRO3 on atopy, asthma, and allergic rhinitis using 1168 unrelated Japanese adults who had GWAS genotyping. We then examined the genetic impact of rs2297377 (TYRO3) on atopy and allergic rhinitis in 2 other independent Japanese populations. A meta-analysis of 3 Japanese populations (a total of 2403 Japanese adults) revealed that rs2297377 was associated with atopy and allergic rhinitis (OR = 1.29 and 1.31; P = 0.00041 and 0.0010, respectively). The risk allele at rs2297377 correlated with decreased expression of TYRO3 mRNA. The gene-gene interaction between HLA-DPB1 and TYRO3 was not significant with regard to sensitization. The estimated proportion of atopy and allergic rhinitis cases attributable to the risk genotype was 14% and 16%, respectively. Our study identified TYRO3 as an important susceptibility gene to atopy and allergic rhinitis in Japanese.
Sections du résumé
BACKGROUND
BACKGROUND
TYRO3 is a member of the TAM (TYRO3, AXL, MERTK) receptor tyrosine kinase family and functions to limit type 2 immune responses implicated in allergic sensitization. Recent studies have shown that multiple intronic variants of TYRO3 were associated with asthma, implying that genetic variation could contribute to errant immune activation. We therefore hypothesized that expression quantitative trait loci (eQTLs) of the TYRO3 gene influence the development of allergic diseases (including asthma and allergic rhinitis) in Japanese populations.
METHODS
METHODS
We performed a candidate gene case-control association study of 8 eQTLs of TYRO3 on atopy, asthma, and allergic rhinitis using 1168 unrelated Japanese adults who had GWAS genotyping. We then examined the genetic impact of rs2297377 (TYRO3) on atopy and allergic rhinitis in 2 other independent Japanese populations.
RESULTS
RESULTS
A meta-analysis of 3 Japanese populations (a total of 2403 Japanese adults) revealed that rs2297377 was associated with atopy and allergic rhinitis (OR = 1.29 and 1.31; P = 0.00041 and 0.0010, respectively). The risk allele at rs2297377 correlated with decreased expression of TYRO3 mRNA. The gene-gene interaction between HLA-DPB1 and TYRO3 was not significant with regard to sensitization. The estimated proportion of atopy and allergic rhinitis cases attributable to the risk genotype was 14% and 16%, respectively.
CONCLUSIONS
CONCLUSIONS
Our study identified TYRO3 as an important susceptibility gene to atopy and allergic rhinitis in Japanese.
Identifiants
pubmed: 30082152
pii: S1323-8930(18)30087-X
doi: 10.1016/j.alit.2018.07.004
pii:
doi:
Substances chimiques
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
TYRO3 protein, human
EC 2.7.10.1
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
77-81Informations de copyright
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