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論文
- タイトル
- タイトル（英）
- Drug-induced cis-regulatory elements in human hepatocytes affect molecular phenotypes associated with adverse reactions
- 参照URL
- https://researchmap.jp/hkawaji/published_papers/49915229
- 著者
- 著者（英）
- Saki Gotoh-Saito,Ryoko Wada,Hideya Kawaji
- 担当区分
- 概要
- 概要（英）
- Genomic variation drives phenotypic diversity, including individual differences in drug response. While coding polymorphisms linked to drug efficacy and adverse reactions are well characterized, the contribution of noncoding regulatory elements remains underexplored. Using CAGE (Cap Analysis of Gene Expression), profiling transcription initiations of mRNAs and enhancer RNAs, we identify candidate cis-regulatory elements (CREs) and assessed their activities simultaneously in HepG2 cells expressing the drug-responsive transcription factor pregnane X receptor (PXR). Comparison with GWAS data reveals strong enrichment of the drug-induced CREs near variants associated with bilirubin and vitamin D levels. Among those bound by PXR in primary hepatocytes, we identify enhancers of UGT1A1, TSKU, and CYP24A1 and functional alleles that alter regulatory activities. We also find that TSKU influences expression of vitamin D-metabolizing enzymes. This study expands the landscape of PXR-mediated regulatory elements and uncovers noncoding variants impacting drug response, providing insights into the genomic basis of adverse drug reactions.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Nature communications
- 巻
- 16
- 号
- 1
- 開始ページ
- 3851
- 終了ページ
- 3851
- 出版年月
- 2024年7月24日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1101/2024.07.24.604883
- 共同研究・競争的資金等の研究課題
研究者
川路 英哉
( )