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Title: NELFCD and CTSZ loci are associated with jaundice-stage progression in primary biliary cholangitis in the Japanese population
Authors: Nishida, Nao
Aiba, Yoshihiro
Hitomi, Yuki
Kawashima, Minae
Kojima, Kaname
Kawai, Yosuke
Ueno, Kazuko
Nakamura, Hitomi
Yamashiki, Noriyo  kyouindb  KAKEN_id
Tanaka, Tomohiro
Tamura, Sumito
Mori, Akira
Yagi, Shintaro  kyouindb  KAKEN_id  orcid (unconfirmed)
Soejima, Yuji
Yoshizumi, Tomoharu
Takatsuki, Mitsuhisa
Tanaka, Atsushi
Harada, Kenichi
Shimoda, Shinji
Komori, Atsumasa
Eguchi, Susumu
Maehara, Yoshihiko
Uemoto, Shinji  kyouindb  KAKEN_id
Kokudo, Norihiro
Nagasaki, Masao  kyouindb  KAKEN_id  orcid (unconfirmed)
Tokunaga, Katsushi
Nakamura, Minoru
Author's alias: 八木, 真太郎
上本, 伸二
Issue Date: 23-May-2018
Publisher: Springer Nature
Journal title: Scientific reports
Volume: 8
Thesis number: 8071
Abstract: Approximately 10–20% of patients with primary biliary cholangitis (PBC) progress to jaundice stage regardless of treatment with ursodeoxycholic acid and bezafibrate. In this study, we performed a GWAS and a replication study to identify genetic variants associated with jaundice-stage progression in PBC using a total of 1, 375 patients (1, 202 early-stage and 173 jaundice-stage) in a Japanese population. SNP rs13720, which is located in the 3′UTR of cathepsin Z (CTSZ), showed the strongest association (odds ratio [OR] = 2.15, P = 7.62 × 10⁻⁷) with progression to jaundice stage in GWAS. High-density association mapping at the CTSZ and negative elongation factor complex member C/D (NELFCD) loci, which are located within a strong linkage disequilibrium (LD) block, revealed that an intronic SNP of CTSZ, rs163800, was significantly associated with jaundice-stage progression (OR = 2.16, P = 8.57 × 10⁻⁸). In addition, eQTL analysis and in silico functional analysis indicated that genotypes of rs163800 or variants in strong LD with rs163800 influence expression levels of both NELFCD and CTSZ mRNA. The present novel findings will contribute to dissect the mechanism of PBC progression and also to facilitate the development of therapies for PBC patients who are resistant to current therapies.
Rights: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI(Published Version): 10.1038/s41598-018-26369-6
PubMed ID: 29795304
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