Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387296095> ?p ?o ?g. }
- W4387296095 abstract "Abstract Background Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced DNAm changes in airway epithelial cells, and assess potential functional consequences and the influence of genetic variation and asthma-related clinical variables. Results We followed a discovery and validation study design to characterize albuterol-induced DNAm changes in paired airway epithelial cultures stimulated in vitro with albuterol. In the discovery phase, an epigenome-wide association study using paired nasal epithelial cultures from Puerto Rican children ( n = 97) identified 22 CpGs genome-wide associated with repeated-use albuterol treatment ( p < 9 × 10 –8 ). Albuterol predominantly induced a hypomethylation effect on CpGs captured by the EPIC array across the genome (probability of hypomethylation: 76%, p value = 3.3 × 10 –5 ). DNAm changes on the CpGs cg23032799 ( CREB3L1 ), cg00483640 ( MYLK4-LINC01600 ), and cg05673431 ( KSR1 ) were validated in nasal epithelia from 10 independent donors (false discovery rate [FDR] < 0.05). The effect on the CpG cg23032799 ( CREB3L1 ) was cross-tissue validated in bronchial epithelial cells at nominal level ( p = 0.030). DNAm changes in these three CpGs were shown to be influenced by three independent genetic variants (FDR < 0.05). In silico analyses showed these polymorphisms regulated gene expression of nearby genes in lungs and/or fibroblasts including KSR1 and LINC01600 (6.30 × 10 –14 ≤ p ≤ 6.60 × 10 –5 ). Additionally, hypomethylation at the CpGs cg10290200 ( FLNC ) and cg05673431 (KSR1 ) was associated with increased gene expression of the genes where they are located (FDR < 0.05). Furthermore, while the epigenetic effect of albuterol was independent of the asthma status, severity, and use of medication, BDR was nominally associated with the effect on the CpG cg23032799 ( CREB3L1) ( p = 0.004). Gene-set enrichment analyses revealed that epigenomic modifications of albuterol could participate in asthma-relevant processes (e.g., IL-2, TNF-α, and NF-κB signaling pathways). Finally, nine differentially methylated regions were associated with albuterol treatment, including CREB3L1 , MYLK4 , and KSR1 (adjusted p value < 0.05). Conclusions This study revealed evidence of epigenetic modifications induced by albuterol in the mucociliary airway epithelium. The epigenomic response induced by albuterol might have potential clinical implications by affecting biological pathways relevant to asthma." @default.
- W4387296095 created "2023-10-04" @default.
- W4387296095 creator A5005988117 @default.
- W4387296095 creator A5011138595 @default.
- W4387296095 creator A5011939088 @default.
- W4387296095 creator A5014565144 @default.
- W4387296095 creator A5016623141 @default.
- W4387296095 creator A5024377581 @default.
- W4387296095 creator A5040011686 @default.
- W4387296095 creator A5040883447 @default.
- W4387296095 creator A5052447524 @default.
- W4387296095 creator A5053206767 @default.
- W4387296095 creator A5057537193 @default.
- W4387296095 creator A5057830517 @default.
- W4387296095 creator A5059093059 @default.
- W4387296095 creator A5067060534 @default.
- W4387296095 creator A5072896022 @default.
- W4387296095 creator A5080971226 @default.
- W4387296095 creator A5088861717 @default.
- W4387296095 date "2023-10-03" @default.
- W4387296095 modified "2023-10-18" @default.
- W4387296095 title "Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells" @default.
- W4387296095 cites W1465453806 @default.
- W4387296095 cites W1516022962 @default.
- W4387296095 cites W1612417873 @default.
- W4387296095 cites W1951464467 @default.
- W4387296095 cites W1967701134 @default.
- W4387296095 cites W1979594866 @default.
- W4387296095 cites W1983551875 @default.
- W4387296095 cites W1985895058 @default.
- W4387296095 cites W1990714059 @default.
- W4387296095 cites W2007662250 @default.
- W4387296095 cites W2008369070 @default.
- W4387296095 cites W2010507765 @default.
- W4387296095 cites W2010882238 @default.
- W4387296095 cites W2020473420 @default.
- W4387296095 cites W2022875135 @default.
- W4387296095 cites W2041257252 @default.
- W4387296095 cites W2042421957 @default.
- W4387296095 cites W2057930810 @default.
- W4387296095 cites W2069185928 @default.
- W4387296095 cites W2069595758 @default.
- W4387296095 cites W2079029414 @default.
- W4387296095 cites W2084286208 @default.
- W4387296095 cites W2100158750 @default.
- W4387296095 cites W2100697281 @default.
- W4387296095 cites W2105791826 @default.
- W4387296095 cites W2107424466 @default.
- W4387296095 cites W2115937056 @default.
- W4387296095 cites W2123929789 @default.
- W4387296095 cites W2129430544 @default.
- W4387296095 cites W2129958809 @default.
- W4387296095 cites W2146512944 @default.
- W4387296095 cites W2153236387 @default.
- W4387296095 cites W2156096560 @default.
- W4387296095 cites W2166623089 @default.
- W4387296095 cites W2169353806 @default.
- W4387296095 cites W2170599998 @default.
- W4387296095 cites W2179438025 @default.
- W4387296095 cites W2187583278 @default.
- W4387296095 cites W2197124664 @default.
- W4387296095 cites W2228635522 @default.
- W4387296095 cites W2238861146 @default.
- W4387296095 cites W2241686927 @default.
- W4387296095 cites W2309685155 @default.
- W4387296095 cites W2338611800 @default.
- W4387296095 cites W2345356016 @default.
- W4387296095 cites W2346059151 @default.
- W4387296095 cites W2347182889 @default.
- W4387296095 cites W2407182836 @default.
- W4387296095 cites W2468927249 @default.
- W4387296095 cites W2517700447 @default.
- W4387296095 cites W2529024004 @default.
- W4387296095 cites W2561881877 @default.
- W4387296095 cites W2580897959 @default.
- W4387296095 cites W2592811885 @default.
- W4387296095 cites W2793679678 @default.
- W4387296095 cites W2806514843 @default.
- W4387296095 cites W2810953028 @default.
- W4387296095 cites W2940564010 @default.
- W4387296095 cites W2943909458 @default.
- W4387296095 cites W2944944066 @default.
- W4387296095 cites W2952330285 @default.
- W4387296095 cites W2957018670 @default.
- W4387296095 cites W2972495016 @default.
- W4387296095 cites W2973599212 @default.
- W4387296095 cites W2990083992 @default.
- W4387296095 cites W3005854090 @default.
- W4387296095 cites W3015695162 @default.
- W4387296095 cites W3026537720 @default.
- W4387296095 cites W3110794024 @default.
- W4387296095 cites W3137645651 @default.
- W4387296095 cites W3140207009 @default.
- W4387296095 cites W3182748185 @default.
- W4387296095 cites W3183384356 @default.
- W4387296095 cites W3183486813 @default.
- W4387296095 cites W4200382074 @default.
- W4387296095 cites W4205588008 @default.
- W4387296095 cites W4232909036 @default.
- W4387296095 cites W4239218095 @default.