Identification of differentially methylated genes for severe acne by genome-wide DNA methylation and gene expression analysis

Wang, Huai; Dang, Tianyuan; Feng, Jiaqi; Wu, Wenjuan; He, Li; Yang, Jiankang

doi:10.1080/15592294.2023.2199373

Cited by 4 publications

(5 citation statements)

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“…They were detected using the Illumina Infinium Methylation EPIC BeadChip, which can quantitatively measure more than 865,911 methylation sites. We described the methylation assay for each sample in a previous study ( 15 ), from which we obtained 23 differentially methylated loci significantly associated with severe acne ( Supplementary Table S2 ).…”

Section: Methodsmentioning

confidence: 99%

“…Although there are still few studies on DNA methylation associated with severe acne, several inflammatory skin diseases, including psoriasis and systemic lupus erythematosus, have been found to be associated with DNA methylation, from which we infer that DNA methylation may play an influential role in the development of severe acne ( 13 , 14 ). A previous study identified 23 differentially methylated probes (DMPs) associated with severe acne ( 15 ). However, the potential mechanism by which these methylation markers are associated with severe acne is not clear.…”

Section: Introductionmentioning

confidence: 99%

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DNA methylation mediated genetic risk in severe acne in a young men population

Wu¹,

Chen²,

Bo³

et al. 2023

Front. Med.

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BackgroundAcne is a chronic inflammatory skin disease that affects the pilosebaceous follicle and is influenced by heredity, hormones, inflammation, and the environment. At present, the recognized pathogenesis mainly includes four categories: excessive sebum secretion, excessive Cutibacterium acnes proliferation, excessive keratinization of sebaceous glands in hair follicles, and inflammatory mechanisms. Previous studies have found that DNA methylation is closely related to some chronic inflammatory skin diseases, and there is evidence that DNA methylation is controlled by genetic factors, making us want to know the relationship between DNA methylation, genetic variation and acne.Materials and methodsIn our previous study, we performed genome-wide DNA methylation analysis in peripheral blood samples from 44 patients with severe acne and 44 unaffected normal subjects, and identified 23 differentially methylated probes (DMPs). In this study, we identified single nucleotide polymorphisms (SNPs) associated with severe acne by genome-wide association analysis in these 88 samples. To test the association between SNPs and DMPs, we conducted DNA methylation quantitative trait loci (methQTL) analysis. Next, causal inference testing (CIT) was used to determine whether genetic variation influences DNA methylation, which impacts disease phenotypes.ResultWe found 38,269 SNPs associated with severe acne. By methQTL analysis, we obtained 24 SNP-CpG pairs that reached the threshold (FDR < 0.05), which included 7 unique CpGs and 22 unique methQTL SNPs. After CIT analysis, we found that 11 out of 24 pairs of SNP-CpG showed a weakened SNP effect after adjustment for methylation, indicating a methylation-mediated relationship between SNPs and severe acne. These 11 SNP-CpG pairs consist of four unique CpG sites and 11 SNPs, of which three CpG sites, cg03020863, cg20652636, and cg19964325, are located on the gene body of PDGFD, the intron of SH2D6, and the 5’UTR of the IL1R1 gene, respectively.ConclusionDuring this study, the DNA methylation of certain genes was found to be influenced by genetic factors and mediated the risk of severe acne in a young Chinese male population, providing a new perspective on the pathogenesis of severe acne.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DNA methylation mediated genetic risk in severe acne in a young men population

Wu¹,

Chen²,

Bo³

et al. 2023

Front. Med.

Self Cite

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“…The phosphorylation by AKT of the p53-binding factor MDM2 promotes p53 degradation, whereas isotretinoin treatment enhances the expression of p53, FoxO1 and FoxO3 in sebaceous glands of acne patients. A recent Chinese epigenetics study identified 23 differentially methylated sites related to severe acne, involving multiple genes such as PDGFD (platelet-derived growth factor D), ARHGEF10 (rho guanine nucleotide exchange factor 10), IL1R1 (IL-1 receptor), PARP8 (poly ADP-ribose polymerase 8), MAPKAPK2 (MAP kinase-activated protein kinase 2), MUC8 (mucin isoform secreted in the endometrium and endocervix), NAV1 (neuron navigator 1), KCNT2 (Na + -activated K + channel T2 or slick channel), and Wnt9A (an embryogenetic differentiation and patterning factor of the Wnt family) [72]. Another recent study performed a DNA methylation and multi-omics analysis of acne skin samples, finding 31,134 differentially methylated sites and 770 differentially methylated genes with changes in expression [73].…”

Section: Genetic Insights In Afa and Pcosmentioning

confidence: 99%

Adult Female Acne: Recent Advances in Pathophysiology and Therapeutic Approaches

Amuzescu,

Tampa,

Matei

et al. 2024

Cosmetics

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Adult acne is a chronic inflammatory disease of the pilosebaceous unit characterized by the excessive production of abnormal sebum favoring an imbalance of the skin microbiota and the hyperproliferation of Cutibacterium acnes and other virulent microbial strains, leading to an inflammatory environment, innate immunity overactivation, and keratinocyte hyperproliferation in hair follicles pores. Degraded keratinocytes plug the pores, consequently forming microcomedons, which can later evolve to papules, nodules, pustules and scars. Distinct from juvenile acne, in adult female acne (AFA) the symptomatology occurs or persists in postadolescence (after age 25). Although hyperandrogenism or the excessive sensitivity of androgen receptors are the main causes, AFA can be triggered by multiple factors, either including or not including androgen disturbances. The prevalence in adult women is 15–20%. Hyperandrogenism is present in 50% of cases; 70% of hyperandrogenism cases feature polycystic ovary syndrome (PCOS), a complex endocrine and metabolic condition. Genetic susceptibility occurs in 80% of acne cases, often with familial inheritance. Beyond classical stepwise therapeutic protocols (topical agents, isotretinoin, antibiotics, hormonal therapy with estrogens, progestins, spironolactone), novel approaches include the highly effective topical antiandrogen clascoterone, the management of insulin resistance by diet, exercise, stress avoidance, and adjuvant therapies such as berberine. Vaccines against the pathogenic proinflammatory C. acnes hyaluronidase A are in development.

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“…Advances in genomics and transcriptomics, alongside highthroughput sequencing technologies, have ushered in an era of in-depth exploration into the genetic landscape of acne. [12][13][14] The advent of recent advances in genomics, transcriptomics, and bioinformatics tools has enabled in-depth exploration into the genetic landscape of acne, emphasizing the role of differentially expressed genes (DEGs) in its pathology. [15][16][17] Such technological progress, particularly in transcriptomic analyses, offers a deeper understanding of the molecular and genetic landscapes of acne, potentially unveiling diagnostic markers and therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

“…Advances in genomics and transcriptomics, alongside high‐throughput sequencing technologies, have ushered in an era of in‐depth exploration into the genetic landscape of acne 12–14 . The advent of recent advances in genomics, transcriptomics, and bioinformatics tools has enabled in‐depth exploration into the genetic landscape of acne, emphasizing the role of differentially expressed genes (DEGs) in its pathology 15–17 .…”

Section: Introductionmentioning

confidence: 99%

Integrative bioinformatics and experimental validation of hub genetic markers in acne vulgaris: Toward personalized diagnostic and therapeutic strategies

Lin,

Cai,

et al. 2024

J of Cosmetic Dermatology

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BackgroundAcne vulgaris is a widespread chronic inflammatory dermatological condition. The precise molecular and genetic mechanisms of its pathogenesis remain incompletely understood. This research synthesizes existing databases, targeting a comprehensive exploration of core genetic markers.MethodsGene expression datasets (GSE6475, GSE108110, and GSE53795) were retrieved from the GEO. Differentially expressed genes (DEGs) were identified using the limma package. Enrichment analyses were conducted using GSVA for pathway assessment and clusterProfiler for GO and KEGG analyses. PPI networks and immune cell infiltration were analyzed using the STRING database and ssGSEA, respectively. We investigated the correlation between hub gene biomarkers and immune cell infiltration using Spearman's rank analysis. ROC curve analysis validated the hub genes' diagnostic accuracy. miRNet, TarBase v8.0, and ChEA3 identified miRNA/transcription factor–gene interactions, while DrugBank delineated drug–gene interactions. Experiments utilized HaCaT cells stimulated with Propionibacterium acnes, treated with retinoic acid and methotrexate, and evaluated using RT‐qPCR, ELISA, western blot, lentiviral transduction, CCK‐8, wound‐healing, and transwell assays.ResultsThere were 104 genes with consistent differences across the three datasets of paired acne and normal skin. Functional analyses emphasized the significant enrichment of these DEGs in immune‐related pathways. PPI network analysis pinpointed hub genes PTPRC, CXCL8, ITGB2, and MMP9 as central players in acne pathogenesis. Elevated levels of specific immune cell infiltration in acne lesions corroborated the inflammatory nature of the disease. ROC curve analysis identified the acne diagnostic potential of four hub genes. Key miRNAs, particularly hsa‐mir‐124‐3p, and central transcription factors like TFEC were noted as significant regulators. In vitro validation using HaCaT cells confirmed the upregulation of hub genes following Propionibacterium acnes exposure, while CXCL8 knockdown reduced pro‐inflammatory cytokines, cell proliferation, and migration. DrugBank insights led to the exploration of retinoic acid and methotrexate, both of which mitigated gene expression upsurge and inflammatory mediator secretion.ConclusionThis comprehensive study elucidated pivotal genes associated with acne pathogenesis, notably PTPRC, CXCL8, ITGB2, and MMP9. The findings underscore potential biomarkers, therapeutic targets, and the therapeutic potential of agents like retinoic acid and methotrexate. The congruence between bioinformatics and experimental validations suggests promising avenues for personalized acne treatments.

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Identification of differentially methylated genes for severe acne by genome-wide DNA methylation and gene expression analysis

Cited by 4 publications

References 48 publications

DNA methylation mediated genetic risk in severe acne in a young men population

DNA methylation mediated genetic risk in severe acne in a young men population

Adult Female Acne: Recent Advances in Pathophysiology and Therapeutic Approaches

Integrative bioinformatics and experimental validation of hub genetic markers in acne vulgaris: Toward personalized diagnostic and therapeutic strategies

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