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Novel insights into the whole blood DNA methylome of asthma in ethnically diverse children and youth
PP-PDPI, 08 Okt 2023 07:12:38

Esther Herrera-Luis, Carlos de la Rosa-Baez, Scott Huntsman, Celeste Eng, Kenneth B. Beckman, Michael A. Lenoir, Jose Rodriguez-Santana, Jesús Villar, Catherine Laprise, Luisa N. Borrell, Elad Ziv, Esteban G. Burchard, Maria Pino-Yanes

European Respiratory Journal 2023; DOI: 10.1183/13993003.00714-2023

Abstract

Rationale The epigenetic mechanisms of asthma remain largely understudied in African Americans and Hispanics/Latinos, two populations disproportionately affected by asthma. We aimed to identify markers, regions, and processes with differential patterns of DNA methylation (DNAm) in whole blood by asthma status in ethnically diverse children and youth, and to assess their functional consequences.

Methods DNAm levels were profiled with the Infinium EPIC or the HumanMethylation450 BeadChip arrays among 1226 African Americans or Hispanics/Latinos and assessed for differential methylation per asthma status at the CpG or region (DMR) level. Novel associations were validated in blood and/or nasal epithelium from ethnically diverse children and youth. The functional and biological implications of the markers identified were investigated by combining epigenomics with transcriptomics from study participants.

Results 128 CpGs and 196 DMRs were differentially methylated after multiple testing corrections, including 92.3% and 92.8% novel associations, respectively. Forty-one CpGs were replicated in other Hispanics/Latinos, prioritizing cg17647904 (NCOR2) and cg16412914 (AXIN1) as asthma DNAm markers. Significant DNAm markers were enriched in previous associations for asthma, fractional exhaled nitric oxide, bacterial infections, immune regulation, or eosinophilia. Functional annotation highlighted epigenetically-regulated gene networks involved in corticosteroid response, host defense, and immune regulation. Several implicated genes are targets for approved or experimental drugs, including TNNC1 and NDUFA12. Many differentially methylated loci previously associated with asthma were validated in our study.

Conclusions We report novel whole-blood DNAm markers for asthma underlying key processes of the disease pathophysiology and confirm the transferability of previous asthma DNAm associations to ethnically diverse populations.

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