Genetic variants in Hippo pathway genes are associated with house dust mite-induced allergic rhinitis in a Chinese population.

Abstract

BackgroundHouse 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.MethodsForty‐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.ResultsWe 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.ConclusionOur findings indicated that rs754466 in DLG5 decreased the susceptibility to HDM‐induced AR.