Journal
ISCIENCE
Volume 26, Issue 8, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2023.107383
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This study conducted comprehensive bioinformatics analyses and experimental verifications to explore the regulatory mechanism of rs10516526 and GSTCD in COPD. The results showed that low expression of GSTCD was associated with COPD, and the transcription factors C-Jun and CREB1 were found to be essential for the regulation of GSTCD by specific genetic signals. Moreover, certain mutated forms of these signals showed a stronger binding ability to the transcription factors, potentially leading to allele-specific regulation and reduced susceptibility to COPD.
Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is influenced by genetic factors. The genetic signal rs10516526 in the glutathione S-transferase C-terminal domain containing (GSTCD) gene is a highly significant and reproducible signal associated with lung function and COPD on chromosome 4q24. In this study, comprehensive bioinformatics analyses and experimental verifications were detailly implemented to explore the regulation mechanism of rs10516526 and GSTCD in COPD. The results suggested that low expression of GSTCD was associated with COPD (p = 0.010). And C-Jun and CREB1 transcription factors were found to be essential for the regulation of GSTCD by rs80245547 and rs72673891. Moreover, rs80245547T and rs72673 891G had a stronger binding ability to these transcription factors, which may promote the allele-specific long-range enhancer-promoter interactions on GSTCD, thus making COPD less susceptible. Our study provides a new insight into the relationship between rs10516526, GSTCD, and COPD.
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