Identification of rare variants of allergic rhinitis based on whole genome sequencing and gene expression profiling: A preliminary investigation in four families

Abstract

Background Despite the success of genome-wide association studies for allergic rhinitis (AR), no definitive causal variants have been identified, and a substantial portion of the heritability of the disease is yet to be discovered. Methods Four families, each with at least 1 parent and one child suffering from dust mite (DM) AR, were recruited, and whole-genome sequencing was performed on samples from 9 eligible individuals from these families. Conjoint analysis was performed for existing gene expression profiling data in the literature and the whole genome sequencing data obtained for these individuals; for presence of family-specific variants segregating with AR and the pathways involved. Similar analyses were also performed with data obtained for 96 sporadic house dust mite (HDM) AR patients and 96 healthy controls. Results Three rare variants in three genes (FLT1_c.603A ​> ​T; VEGFB_c.322A ​> ​C; and ITGA2_c.502+1G ​> ​A), which are involved in Focal Adhesion pathway, were identified in affected, but not unaffected, subjects in two families. VEGFB_c.322A ​> ​C and/or ITGA2_c.502+1G ​> ​A were further detected in all DM AR patients but not in any healthy individuals in 1 family; which was further investigated for members. The 3 identified variants were not found in any of the sporadic DM AR patients or healthy controls. Conclusion Despite the relatively small sample size, this study has identified several potentially functional rare variants in AR candidate genes, and it provides a platform for future work in larger numbers of families and sporadic individuals for a better understanding of the genetic basis of AR.

Allergic rhinitis is associated with atmospheric SO2: Follow-up study of children from elementary schools in Ulsan, Korea

“…A recent study also showed a significant increase in the risk of allergic diseases including asthma, allergic rhinitis, and atopic dermatitis, if a parent had a history of allergy [ 77 ]. Research on the association between family history and allergic diseases has been widely conducted, and recent studies have shown the association of specific genetic polymorphism with the susceptibility to allergic rhinitis [ 78 , 79 ].…”

Gene Signatures and Associated Transcription Factors of Allergic Rhinitis: KLF4 Expression Is Associated with Immune Response

“…To date, next-generation sequencing and bioinformatics analysis have been used to identify genetic and transcriptomic alterations involved in the development and progression of the disease and to classify patients for therapeutic prediction [ 6 , 7 ]. Previous studies on AR have focused on genetic and transcriptomic alterations to identify AR-related features and have demonstrated variants of Vascular Endothelial Growth Factor B ( VEGFB , 322A>C) and/or Integrin Subunit Alpha 2 ( ITGA2 , 502+1G>A) mainly in AR patients [ 8 ]. In addition, it was found that expression of the periostin ( POSTN ) gene was enhanced in AR compared to non-AR [ 9 ].…”