Increased epigenetic age acceleration in the hidradenitis suppurativa skin

Lukac, Danitza; Pagani, Kyla; Collender, Philip A.; Fadadu, Raj P.; McGee, Jean S.

doi:10.1007/s00403-022-02432-1

Cited by 4 publications

(3 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The immunopathology of HS includes genetic factors and environmental factors including obesity and smoking (both active and passive) and various epigenetic alterations have been reported. [6][7][8][9][10][11][12] Studies of various large-scale exomes and candidate γ-secretase gene mutations have been reported to have identified ~80 different gene variants involved in HS disease aetiology across the globe, 13,14 as well as genetic heterogeneity. 15 Most variants were detected in patients with a family history of HS, but a small number were also found in sporadic cases.…”

Section: Introductionmentioning

confidence: 99%

Hidradenitis suppurativa associated telomere‐methylome dysregulations in blood

Radhakrishna,

Ratnamala,

Jhala

et al. 2023

Acad Dermatol Venereol

View full text Add to dashboard Cite

BackgroundHidradenitis suppurativa (HS) is a chronic debilitating disease with a significant burden of both organic and psychological comorbidities. It has been shown that certain telomere‐related genes (TRGs) affect a wide range of diseases, including HS and its associated comorbidities, but their exact role in HS pathogenesis is still unknown.ObjectivesTo determine whether TRG methylomes can be used as biomarkers in HS.MethodsUsing the Illumina HumanMethylation450 BeadChip array, we examined methylation variations associated with TRGs in HS cases and age‐, sex‐, and ethnicity‐matched healthy controls. The study utilized integrated bioinformatics statistical methods, such as a false discovery rate (FDR), the area under the receiver operating characteristic curve (AUC), and principal component analysis.ResultsThere were a total of 585 different differentially methylated CpG sites identified in 585 TRGs associated with HS (474 hypomethylated and 111 hypermethylated) (FDR p‐value <0.05). A number of these CpGs have been identified as being involved in increased pain sensitivity including EPAS1, AHR, CSNK1D, DNMT1, IKBKAP, NOS3, PLCB1, and PRDM16 genes; GABRB3 as a potential alcohol addiction marker; DDB1, NSMCE2, and HNRNPA2B1 associated with cancers. Pathway analysis identified 67 statistically significant pathways, including DNA repair, telomere maintenance, mismatch repair, and cell cycle control. (p<0.001).ConclusionThe disruption of TRGs leads to the shortening of telomeres, which is associated with HS progression, aging, cellular senescence, and an increased risk of various diseases, including cancer and associated comorbidities, such as metabolic syndrome, cardiovascular disease, and inflammatory disorders. Further research is necessary to better understand the underlying mechanisms and establish causal links between TRGs and HS. The present study is the first effort to comprehend potential pathomechanisms of sporadic HS cases concentrating on PBMC methylome since ours.

show abstract

Section: Introductionmentioning

confidence: 99%

Hidradenitis suppurativa associated telomere‐methylome dysregulations in blood

Radhakrishna,

Ratnamala,

Jhala

et al. 2023

Acad Dermatol Venereol

View full text Add to dashboard Cite

show abstract

“…Moreover, understanding the interplay between genetic predisposition and epigenetic modifications is of paramount importance. Unraveling how genetic factors and environmental triggers converge to shape the epigenetic landscape in HS offers a holistic perspective on disease etiology [7,13].…”

Section: Introductionmentioning

confidence: 99%

Unraveling the Epigenetic Tapestry: Decoding the Impact of Epigenetic Modifications in Hidradenitis Suppurativa Pathogenesis

Nardacchione,

Tricarico,

Moura

et al. 2023

Genes

View full text Add to dashboard Cite

Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin disorder, which typically occurs during puberty or early adulthood. The pathogenesis of HS is complex and multifactorial; a close interaction between hormonal, genetic, epigenetics factors, host-specific aspects, and environmental influences contributes to the susceptibility, onset, severity, and clinical course of this disease, although the exact molecular mechanisms are still being explored. Epigenetics is currently emerging as an interesting field of investigation that could potentially shed light on the molecular intricacies underlying HS, but there is much still to uncover on the subject. The aim of this work is to provide an overview of the epigenetic landscape involved in HS. Specifically, in this in-depth review we provide a comprehensive overview of DNA methylation/hydroxymethylation, histone modifications, and non-coding RNAs (such as microRNA—miRNA-132, miRNA-200c, miRNA-30a-3p, miRNA-100-5b, miRNA-155-5p, miRNA-338-5p) dysregulation in HS patients. An interesting element of epigenetic regulation in HS is that the persistent inflammatory milieu observed in HS lesional skin could be exacerbated by an altered methylation profile and histone acetylation pattern associated with key inflammatory genes. Deepening our knowledge on the subject could enable the development of targeted epigenetic therapies to potentially restore normal gene expression patterns, and subsequentially ameliorate, or even reverse, the progression of the disease. By deciphering the epigenetic code governing HS, we strive to usher in a new era of personalized and effective interventions for this enigmatic dermatological condition.

show abstract

“…So far, studies linking epigenetic mechanisms with skin inflammatory diseases ( 17 ) are mostly limited to atopic dermatitis and psoriasis ( 18 , 19 ). A recent report linked epigenetic age acceleration with extrinsic immune-related changes in patients with HS ( 20 ). There is a clear knowledge gap in our understanding of the exact role of epigenetic mechanisms in HS pathogenesis.…”

mentioning

confidence: 99%