Abstract
BACKGROUND: House dust mite (HDM)-induced allergic rhinitis (AR) is a highly prevalent disease with bothersome symptoms. Genetic variants of the Hippo pathway genes play a critical role in the respiratory disease. However, no study has reported associations between variants of the Hippo pathway genes and HDM-induced AR risk. METHODS: Forty-three key genes in the Hippo pathway were selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway database, and previous reported studies. A case-control study of 222 cases and 237 controls was performed to assess the associations between 121 genetic variants in these genes and HDM-induced AR risk. DNeasy Blood & Tissues Kits were used for extracting genomic DNA from the venous blood and Infinium Asian Screening Array BeadChips for performing genotyping. A logistic regression model was applied to evaluate the effects of variants on HDM-induced AR risk. The false discovery rate (FDR) method was utilized to correct for multiple testing. The receiver operating characteristic (ROC) curve was plotted to obtain the cut-off value of total IgE for the diagnosis of HDM-induced AR. Histone modification and transcription factor binding sites were visualized by UCSC genome browser. Moreover, expression qualitative trait loci (eQTL) analysis was obtained from Genotype-Tissue Expression (GTEx) database. RESULTS: We found that rs754466 in DLG5 was significantly associated with a decreased HDM-induced AR risk after FDR correction (adjusted odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36-0.74, p = 3.25 × 10(-4) , P(FDR) = 3.93 × 10(-2) ). The rs754466 A allele reduced the risk of HDM-induced AR in the subgroup of moderate/severe total nasal symptom score (TNSS). Furthermore, rs754466 was associated with a high mRNA expression of DLG5. Additionally, histone modification and transcription factor binding sites were rich in the region containing rs754466. CONCLUSION: Our findings indicated that rs754466 in DLG5 decreased the susceptibility to HDM-induced AR.