Association analyses of eQTLs of the <i>TYRO3</i> gene and allergic diseases in Japanese populations

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<p><i>Background:</i> <i>TYRO3</i> is a member of the TAM (<i>TYRO3</i>, <i>AXL</i>, <i>MERTK</i>) 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 <i>TYRO3</i> 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 <i>TYRO3</i> gene influence the development of allergic diseases (including asthma and allergic rhinitis) in Japanese populations.</p><p><i>Methods:</i> We performed a candidate gene case-control association study of 8 eQTLs of <i>TYRO3</i> on atopy, asthma, and allergic rhinitis using 1168 unrelated Japanese adults who had GWAS genotyping. We then examined the genetic impact of rs2297377 (<i>TYRO3</i>) on atopy and allergic rhinitis in 2 other independent Japanese populations.</p><p><i>Results:</i> <i>A</i> 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 <i>TYRO3</i> mRNA. The gene-gene interaction between <i>HLA-DPB1</i> and <i>TYRO3</i> 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.</p><p><i>Conclusions:</i> Our study identified <i>TYRO3</i> as an important susceptibility gene to atopy and allergic rhinitis in Japanese.</p>


  • Allergology International

    Allergology International 68(1), 77-81, 2019

    Japanese Society of Allergology


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