Genome-wide DNA methylation profile of peripheral blood lymphocytes from subjects with nonsteroidal anti-inflammatory drug-induced respiratory diseases.
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 ANDMETHODS:
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.
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