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Genome-wide DNA methylation profile of peripheral blood lymphocytes from subjects with nonsteroidal anti-inflammatory drug-induced respiratory diseases.
Lee, Jong-Uk; Soo Chang, Hun; Kyung Kim, Min; Park, Seung-Lee; Kim, Jung Hyun; Park, Jong-Sook; Park, Choon-Sik.
Afiliación
  • Lee JU; Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital.
  • Soo Chang H; Department of Anatomy and BK21 FOUR Project, College of Medicine, Soonchunhyang University, Cheonan.
  • Kyung Kim M; Department of Interdisciplinary Program in Biomedical Science Major, Soonchuhyang University.
  • Park SL; Department of Interdisciplinary Program in Biomedical Science Major, Soonchuhyang University.
  • Kim JH; Department of Internal Medicine, Korean Armed Forces Capital Hospital, Seongnam.
  • Park JS; Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital.
  • Park CS; Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital.
Pharmacogenet Genomics ; 32(6): 226-234, 2022 08 01.
Article en En | MEDLINE | ID: mdl-35696287
ABSTRACT

BACKGROUND:

Significant changes in CpG methylation have been identified in nasal polyps, which are the main targets of nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD); however, these polyps are composed of various cellular components. In the present study, whole-genome CpG methylation in peripheral blood lymphocytes (PBLs) was analyzed to define the epigenetic changes in lymphocytes, which are the primary immune cells involved in NERD. MATERIALS AND

METHODS:

Genomic DNA from peripheral blood mononuclear cells from 27 NERD and 24 aspirin-tolerant asthma (ATA) was subjected to bisulfate conversion and a methylation array. Quantitative CpG methylation, the ß-values as a quantitative measure of DNA methylation, in lymphocytes were calculated after adjustments for cellular composition.

RESULTS:

Fifty-six hypermethylated and three hypomethylated differentially methylated CpGs (DMCs) in PBLs in the NERD compared with ATA. The top 10 CpG loci predicted the methylation risk score, with a positive predictive value of 91.3%, a negative predictive value of 81.5% and an accuracy of 84.3%. As demonstrated in the nasal polyps, 30 DMCs were predicted to bind to the following 10 transcription factors, ranked in descending order AP-2alphaA, TFII-1, STAT4, FOXP3, GR, c-Est-1, E2F-1, XBP1, ENKTF-1 and NF-1. Gene ontology analysis identified 13 categories such as regulation of T-helper 17 cell differentiation, including SMAD7 and NFKBIZ. PBLs in NERD contained no DMCs in genes associated with the prostaglandin and leukotriene pathways, which were found in ATA.

CONCLUSION:

PBLs in NERD form a unique pattern of DNA CpG methylation, and the combined analysis may provide predictive values for NERD.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Asma / Pólipos Nasales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Pharmacogenet Genomics Asunto de la revista: FARMACOLOGIA / GENETICA MEDICA Año: 2022 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Asma / Pólipos Nasales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Pharmacogenet Genomics Asunto de la revista: FARMACOLOGIA / GENETICA MEDICA Año: 2022 Tipo del documento: Article