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Genome-Wide DNA Methylation and Gene Expression in Patients with Indolent Systemic Mastocytosis

Abstrakt

Mastocytosis is a clinically heterogenous, usually acquired disease of the mast cells with a survival time that depends on the time of onset. It ranges from skin-limited to systemic disease, including indolent and more aggressive variants. The presence of the oncogenic KIT p. D816V gene somatic mutation is a crucial element in the pathogenesis. However, further epigenetic regulation may also affect the expression of genes that are relevant to the pathology. Epigenetic alterations are re-sponsible for regulating the expression of genes that do not modify the DNA sequence. In general, it is accepted that DNA methylation inhibits the binding of transcription factors, thereby down-regulating gene expression. However, so far, little is known about the epigenetic factors leading to the clinical onset of mastocytosis. Therefore, it is essential to identify possible epigenetic predictors, indicators of disease progression, and their link to the clinical picture to establish appropriate management and a therapeutic strategy. The aim of this study was to analyze genome-wide methylation profiles to identify differentially methylated regions (DMRs) in patients with mastocytosis compared to healthy individuals, as well as the genes located in those regulatory regions. Genome-wide DNA methylation profiling was performed in peripheral blood collected from 80 adult patients with indolent systemic mastocytosis (ISM), the most prevalent subvariant of mastocytosis, and 40 healthy adult volunteers. A total of 117 DNA samples met the criteria for the bisulfide conversion step and microarray analysis. Genome-wide DNA methylation analysis was performed using a MethylationEPIC BeadChip kit. Further analysis was focused on the genomic regions rather than individual CpG sites. Co-methylated regions (CMRs) were assigned via the CoMeBack method. To identify DMRs between the groups, a linear regression model with age as the covariate on CMRs was performed using Limma. Using the available data for cases only, an association analysis was performed between methylation status and tryptase levels, as well as the context of allergy, and anaphylaxis. KEGG pathway mapping was used to identify genes differentially expressed in anaphylaxis. Based on the DNA methylation results, the expression of 18 genes was then analyzed via real-time PCR in 20 patients with mastocytosis and 20 healthy adults. A comparison of the genome-wide DNA methylation profile between the mastocytosis patients and ...

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Accepted albo Published Version
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.3390/ijms241813910
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Creative Commons: CC-BY otwiera się w nowej karcie

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Informacje szczegółowe

Kategoria:
Publikacja w czasopiśmie
Typ:
artykuły w czasopismach
Opublikowano w:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES nr 24,
ISSN: 1661-6596
Język:
angielski
Rok wydania:
2023
Opis bibliograficzny:
Górska A., Urbanowicz M., Grochowalski Ł., Seweryn M., Sobalska-Kwapis M., Wojdacz T. K., Lange M., Gruchała-Niedoszytko M., Jarczak J., Strapagiel D., Górska-Ponikowska M., Pelikant-Malecka I., Kalinowski L., Nedoszytko B., Gutowska-Owsiak D., Niedoszytko M.: Genome-Wide DNA Methylation and Gene Expression in Patients with Indolent Systemic Mastocytosis// INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES -Vol. 24,iss. 18 (2023), s.13910-
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.3390/ijms241813910
Źródła finansowania:
  • Polpharma Scientific Foundation grant no. GUMed/K/735/ 12/2018/231, the Polish Ministry of Education and Science grant no. 10/E-389/SPUB/SP/2020, and the Medical University of Gdansk ST grant no. 01-10023/0004956/01/231/231/0/2023
Weryfikacja:
Politechnika Gdańska

wyświetlono 60 razy

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