Genome-Wide DNA Methylation Profile in Whole Blood of Patients With Chronic Spontaneous Urticaria

Abstract

BackgroundChronic spontaneous urticaria (CSU) is a common autoimmune skin disease. Little is known about the role of epigenetics in the pathogenesis of CSU. This study aimed to investigate genome-wide DNA methylation profile in whole blood of patients with CSU.Patients and MethodsGenome-wide DNA methylation levels in whole blood samples of 95 Chinese Han ethnicity adult CSU patients and 95 ethnicity-, age- and sex-matched healthy controls were analyzed using Illumina 850K methylation chip. The differentially methylated genes (DMGs) were screened out and then functionally annotated by the gene ontology and the Kyoto encyclopedia of genes and genomes databases.ResultsA total of 439 differentially methylated positions (DMPs) (p < 0.01 and |Δβ| ≥ 0.06) were identified with 380 hypomethylated and 59 hypermethylated. The average global DNA methylation levels of the 439 DMPs in the CSU patients were significantly lower than those in the healthy controls (p < 0.001). The distribution of the 439 DMPs was wide on chromosome 1 to 22 and chromosome X. Chromosome 6 embodied the largest number of DMPs (n = 51) and their annotated genes were predominantly related to autoimmunity. The 304 annotated DMGs were mainly enriched in autoimmune disease- and immune-related pathways. A total of 41 DMPs annotated to 28 DMGs were identified when p < 0.01 and |Δβ| ≥ 0.1. Of the 28 DMGs, HLA-DPB2, HLA-DRB1, PPP2R5C, and LTF were associated with autoimmunity. CSU cases with elevated total IgE, positive anti-thyroid peroxidase IgG autoantibodies, positive anti-thyroglobulin IgG autoantibodies, angioedema, UASday > 4, or recurrent CSU showed phenotype-specific DMPs as compared with cases with normal total IgE, negative anti-thyroid peroxidase IgG autoantibodies, negative anti-thyroglobulin IgG autoantibodies, no angioedema, UASday ≤ 4, or non-recurrent CSU respectively.ConclusionThis study shows a distinct genome-wide DNA methylation profile in Chinese Han ethnicity adult CSU patients and indicates a role of epigenetics in the pathogenesis of CSU. The predominant enrichment of the CSU-associated DMGs in immunological pathways provides supportive evidence for the immunopathogenesis of CSU. Future research on the CSU-associated DMPs and DMGs will help discover potential therapeutic targets for CSU.

Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis

“…Subsequently, past research has demonstrated that the distribution of DMPs within the promoter region varies across diseases. In autoimmune diseases, a predominant characteristic is hypomethylated sites in the promoter region DMPs (16,17), a finding that is reinforced by our research. Contrastingly, in carcinoma, hypermethylated sites are more prevalent within promoter region DMPs (18,19).…”

“…Further, DMPs with DNAm levels exceeding 0.7 or falling below 0.3 were selected, as such extreme levels are more likely indicative of lost expression or abundant expression. This approach aids in the discovery of potential biomarkers with functional relevance to disease phenotypes (16). Lastly, prior research has established that methylation patterns of multiple DMPs on promoters constitute key mechanisms influencing gene expression (15).…”

DNA methylation regulatory patterns and underlying pathways behind the co-pathogenesis of allergic rhinitis and chronic spontaneous urticaria

“…The data of genome-wide DNA methylation profile of the AR patients were available at GEO database ( ; GSE50222, n = 32, AR during pollen season = 8, AR outside pollen season = 8, healthy control =16) ( 37 ). The data of genome-wide DNA methylation profile of the CSU patients were available at National Genomics Data Center (NGDC) database ( ; OEP002482, n = 190, CSU = 95, healthy control = 95) ( 34 ). Our workflow for bioinformatics analysis of publicly available datasets from both the GEO and NGDC databases is illustrated in Figure 1 .…”

“…Current research suggested that it may contribute to a variety of cytological processes of T cells in different allergic diseases, including Treg deficiency, TH1 and TH2 polarization, and differentiation of CD4+ T cells (30)(31)(32). Interestingly, researchers have found that some allergic responses of AR or CSU patients can be predicted by the DNA methylation levels when exposed to grass pollen (33,34). In conclusion, the above results indicated that pollen can affect DNA methylation in comorbidity patients, potentially regulating the biological functions of T cells.…”