Genetic Association and Differential RNA Expression of Histone (De)Acetylation-Related Genes in Pemphigus Foliaceus-A Possible Epigenetic Effect in the Autoimmune Response.

Autor: Sulzbach Denardin M; Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil., Bumiller-Bini Hoch V; Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.; Postgraduate Program in Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil., Salviano-Silva A; Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.; Postgraduate Program in Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.; Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany., Lobo-Alves SC; Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.; Research Institut Pelé Pequeno Príncipe, Curitiba 80250-060, Brazil., Adelman Cipolla G; Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil., Malheiros D; Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.; Postgraduate Program in Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil., Augusto DG; Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.; Department of Biological Sciences, The University of North Carolina at Charlotte, Charlotte, NC 28223, USA., Wittig M; Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University of Kiel, 24105 Kiel, Germany., Franke A; Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University of Kiel, 24105 Kiel, Germany., Pföhler C; Department of Dermatology, Saarland University Medical Center, 66421 Homburg, Germany., Worm M; Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergy, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany., van Beek N; Department of Dermatology, University of Lübeck, 23562 Lübeck, Germany., Goebeler M; Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, 97080 Würzburg, Germany., Sárdy M; Department of Dermatology and Allergy, University Hospital, LMU Munich, 80539 Munich, Germany.; Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary., Ibrahim S; College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 127788, United Arab Emirates.; Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, 23562 Lübeck, Germany., Busch H; Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, 23562 Lübeck, Germany., Schmidt E; Department of Dermatology, University of Lübeck, 23562 Lübeck, Germany.; Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, 23562 Lübeck, Germany., Hundt JE; Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, 23562 Lübeck, Germany., Petzl-Erler ML; Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.; Postgraduate Program in Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil., Beate Winter Boldt A; Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.; Postgraduate Program in Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.
Jazyk: angličtina
Zdroj: Life (Basel, Switzerland) [Life (Basel)] 2023 Dec 29; Vol. 14 (1). Date of Electronic Publication: 2023 Dec 29.
DOI: 10.3390/life14010060
Abstrakt: Pemphigus foliaceus (PF) is an autoimmune skin blistering disease characterized by antidesmoglein-1 IgG production, with an endemic form (EPF) in Brazil. Genetic and epigenetic factors have been associated with EPF, but its etiology is still not fully understood. To evaluate the genetic association of histone (de)acetylation-related genes with EPF susceptibility, we evaluated 785 polymorphisms from 144 genes, for 227 EPF patients and 194 controls. Carriers of HDAC4_rs4852054*A were more susceptible (OR = 1.79, p = 0.0038), whereas those with GSE1_rs13339618*A (OR = 0.57, p = 0.0011) and homozygotes for PHF21A_rs4756055*A (OR = 0.39, p = 0.0006) were less susceptible to EPF. These variants were not associated with sporadic PF (SPF) in German samples of 75 SPF patients and 150 controls, possibly reflecting differences in SPF and EPF pathophysiology. We further evaluated the expression of histone (de)acetylation-related genes in CD4 + T lymphocytes, using RNAseq. In these cells, we found a higher expression of KAT2B , PHF20, and ZEB2 and lower expression of KAT14 and JAD1 in patients with active EPF without treatment compared to controls from endemic regions. The encoded proteins cause epigenetic modifications related to immune cell differentiation and cell death, possibly affecting the immune response in patients with PF.
Databáze: MEDLINE
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