Hidradenitis suppurativa associated telomere-methylome dysregulations in blood.

Autor: Radhakrishna U; Department of Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, USA., Ratnamala U; Department of Life Sciences, School of Sciences, Gujarat University, Ahmedabad, India., Jhala DD; Department of Zoology, School of Sciences, Gujarat University, Ahmedabad, India., Uppala LV; College of Information Science & Technology, Peter Kiewit Institute, the University of Nebraska at Omaha, Omaha, Nebraska, USA., Vedangi A; Department of Clinical Research, KIMS ICON Hospital, A Unit of ICON Krishi Institute Medical Sciences, Visakhapatnam, India., Saiyed N; Department of Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, USA., Patel M; Bioinformatics, Gujarat University, Ahmedabad, India., Vadsaria N; Bioinformatics, Gujarat University, Ahmedabad, India., Shah SR; Department of Obstetrics and Gynecology, BJ Medical College Institute of Medical Post-Graduate Studies and Research, Ahmedabad, India., Rawal RM; Department of Life Sciences, School of Sciences, Gujarat University, Ahmedabad, India., Mercuri SR; Unit of Dermatology and Cosmetology, IRCCS San Raffaele Hospital, Milano, Italy., McGonagle D; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK., Jemec GBE; Department of Dermatology, Zealand University Hospital, Roskilde, Denmark., Damiani G; Unit of Dermatology and Cosmetology, IRCCS San Raffaele Hospital, Milano, Italy.; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.; Italian Center of Precision Medicine and Chronic Inflammation, University of Milan, Milan, Italy.
Jazyk: angličtina
Zdroj: Journal of the European Academy of Dermatology and Venereology : JEADV [J Eur Acad Dermatol Venereol] 2024 Feb; Vol. 38 (2), pp. 393-403. Date of Electronic Publication: 2023 Dec 06.
DOI: 10.1111/jdv.19586
Abstrakt: Background: Hidradenitis 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.
Objectives: To determine whether TRG methylomes can be used as biomarkers in HS.
Methods: Using 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.
Results: There 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).
Conclusion: The disruption of TRGs leads to the shortening of telomeres, which is associated with HS progression, ageing, 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.
(© 2023 European Academy of Dermatology and Venereology.)
Databáze: MEDLINE
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