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Allergol Int. 2019 Jan;68(1):77-81. doi: 10.1016/j.alit.2018.07.004. Epub 2018 Aug 3.

Association analyses of eQTLs of the TYRO3 gene and allergic diseases in Japanese populations.

Author information

1
Department of Pulmonary Medicine, University of Tsukuba, Tsukuba, Japan.
2
Department of Pulmonary Medicine, University of Tsukuba, Tsukuba, Japan. Electronic address: hmasuko@md.tsukuba.ac.jp.
3
Tsukuba Medical Center, Tsukuba, Japan.
4
National Hospital Organization Ibarakihigashi National Hospital, Tokai, Japan.
5
Department of Medical Genetics, University of Tsukuba, Tsukuba, Japan.
6
The Jikei University School of Medicine, Tokyo, Japan.

Abstract

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:

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:

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:

Our study identified TYRO3 as an important susceptibility gene to atopy and allergic rhinitis in Japanese.

KEYWORDS:

Allergic rhinitis; Asthma; Atopy; TYRO3; eQTL

PMID:
30082152
DOI:
10.1016/j.alit.2018.07.004
[Indexed for MEDLINE]
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