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Association between DNA hypomethylation at IL 13 gene and allergic rhinitis in house dust mite‐sensitized subjects
Author(s) -
Li J.Y.,
Zhang Y.,
Lin X.P.,
Ruan Y.,
Wang Y.,
Wang C.S.,
Zhang L.
Publication year - 2016
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12647
Subject(s) - dna methylation , methylation , epigenetics , cpg site , immunology , house dust mite , promoter , pathogenesis , gene , real time polymerase chain reaction , allergy , microbiology and biotechnology , medicine , biology , gene expression , allergen , genetics
Summary Background Allergic rhinitis ( AR ) is a complex disease, in which gene–environment interactions contribute to its pathogenesis. Epigenetic modifications such as DNA methylation play an important role in the regulation of gene function. As IL 13 , a pleiotropic cytokine, may be important in conferring susceptibility to AR , the aim of the present work was to assess the relationship between a CpG island methylation status at the upstream of IL 13 gene and house dust mite ( HDM )‐sensitized AR in Han Chinese subjects. Methods A total of 60 patients with HDM ‐sensitized AR and 65 control subjects were enrolled as two independent cohorts from Beijing and Liaoning. Mass ARRAY Epi TYPER and pyrosequencing was used to systematically screen the status of DNA methylation in peripheral blood leucocytes. IL 13 mRNA expression was measured by real‐time quantitative PCR . Electrophoretic mobility shift assay was used to assess the function of methylation site. Results The mean level of methylation was decreased in the AR patient group compared with the control group ( P = 0.01). Two of a total of 33 IL 13 CpG units analysed (CpG units 24 : 25 : 26 and 38 : 39) showed significant differences in methylation status between the AR patient group and the control group, with DNA hypomethylation at CpG38 significantly associated with higher risk of HDM ‐sensitized AR in both independent cohorts and a combined cohort (Beijing: OR = 1.24, 95% CI = 1.01–1.52, P = 0.036; Liaoning: OR = 1.62, 95% CI = 1.11–2.38, P = 0.013; Combined: OR = 1.31, 95% CI = 1.10–1.56, P = 0.002). Methylation level of CpG38 correlated negatively with both IL 13 mRNA expression and serum total IgE level and affected the binding affinity of SP 1. Conclusions DNA hypomethylation of IL 13 gene may be associated with increased risk of AR from HDM sensitization.