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ChIP-seq analysis found IL21R, a target gene of GTF2I–the susceptibility gene for primary biliary cholangitis in Chinese Han

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Abstract

Aims

Aimed to identify a new susceptibility gene associated with primary biliary cholangitis (PBC) in Chinese Han and investigate the possible mechanism of that gene in PBC.

Methods

A total of 466 PBC and 694 healthy controls (HC) were included in our study, and genotyping GTF2I gene variants by Sequenom. CD19 + B cells were isolated for Chromatin immunoprecipitation sequencing (ChIP-seq). Additionally, MEME-ChIP was utilized to perform searches for known motifs and de novo motif discovery. The GTF2I ChIP-seq of hematopoietic cell line (K562) results were obtained from ENCODE (GSE176987, GSE177691). The Genomic HyperBrowser was used to determine overlap and hierarchal clustering between ours and ENCODE datasets.

Results

The frequency of the rs117026326 variant T allele was significantly higher in PBC patients than that in HC (20.26% compared with 13.89%, Pc = 1.09E-04). Furthermore, we observed an elevated proportion of GTF2I binding site located in the upstream and 5ʹ UTR of genes in PBC in comparison with HC. Additionally, an in-depth analysis of IL21R region revealed that GTF2I might bind to the IL21R promoter to regulate the expression of the IL21R, with four peaks of GTF2I binding sites, including three increased binding sites in upstream, one increased binding site in 5' UTR. Motif analysis by MEME-ChIP uncovered five significant motifs. A significant overlap between our ChIP and GSE176987, GSE17769 were found by the Genomic HyperBroswer.

Conclusions

Our study confirmed that GTF2I was associated with PBC in Chinese Han. Furthermore, our gene function analysis indicated that IL21R may be the target gene regulated by GTF2I.

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Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

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Funding

This research was supported by grants from the National Natural Science Foundation of China Grants (81871302, 81801631), and the National Key Research and Development Program of China (2018YFE0207300), Beijing Municipal Science & Technology Commission (Z211100002521021), the National High Level Hospital Clinical Research Funding(2022-PUMCH-B-124,2022-PUMCH-A-007).

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Author notes

  1. Ziyan Wu and Haolong Li have equally contributed to this work.

Authors and Affiliations

  1. Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China

    Ziyan Wu, Haolong Li & Yongzhe Li

  2. Department of Rheumatology and Clinical Immunology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Honglin Xu, Futai Feng, Fengchun Zhang, Shulan Zhang & Li Wang

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  1. Ziyan Wu
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Contributions

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Professor YL had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding authors

Correspondence to Shulan Zhang, Li Wang or Yongzhe Li.

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Conflict of interest

ZW, HL, HX, FF, FZ, SZ, LW, YL declare no conflicts of interest.

Ethical approval

The Ethics Committee of Peking Union Medical College Hospital approved the study protocol (JS-2156).

Informed consent

The informed consent to participate in the ChIP-seq study was provided by the enrolled 3 PBC patients and 3 healthy controls or their families.

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Wu, Z., Li, H., Xu, H. et al. ChIP-seq analysis found IL21R, a target gene of GTF2I–the susceptibility gene for primary biliary cholangitis in Chinese Han. Hepatol Int 18, 509–516 (2024). https://doi.org/10.1007/s12072-023-10586-x

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  • DOI: https://doi.org/10.1007/s12072-023-10586-x

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