Journal article
NELFCD and CTSZ loci are associated with jaundice-stage progression in primary biliary cholangitis in the Japanese population
Scientific reports, Vol.8(May (E-published)), 8071
05/23/2018
DOI: 10.1038/s41598-018-26369-6
PMCID: PMC5966418
PMID: 29795304
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 x 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 x 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.
Details
- Title: Subtitle
- NELFCD and CTSZ loci are associated with jaundice-stage progression in primary biliary cholangitis in the Japanese population
- Creators
- Nao Nishida - The University of TokyoYoshihiro Aiba - Nagasaki Medical CenterYuki Hitomi - The University of TokyoMinae Kawashima - The University of TokyoKaname Kojima - Tohoku Medical Megabank OrganizationYosuke Kawai - Tohoku Medical Megabank OrganizationKazuko Ueno - Tohoku Medical Megabank OrganizationHitomi Nakamura - Nagasaki Medical CenterNoriyo Yamashiki - The University of TokyoTomohiro Tanaka - The University of TokyoSumito Tamura - The University of TokyoAkira Mori - Kyoto UniversityShintaro Yagi - Kyoto UniversityYuji Soejima - Kyushu UniversityTomoharu Yoshizumi - Kyushu UniversityMitsuhisa Takatsuki - Nagasaki UniversityAtsushi Tanaka - Teikyo UniversityKenichi Harada - Kanazawa UniversityShinji Shimoda - Kyushu UniversityAtsumasa Komori - Nagasaki UniversitySusumu Eguchi - Nagasaki UniversityYoshihiko Maehara - Kyushu UniversityShinji Uemoto - Kyoto UniversityNorihiro Kokudo - The University of TokyoMasao Nagasaki - Tohoku Medical Megabank OrganizationKatsushi Tokunaga - The University of TokyoMinoru Nakamura - Nagasaki University
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.8(May (E-published)), 8071
- DOI
- 10.1038/s41598-018-26369-6
- PMID
- 29795304
- PMCID
- PMC5966418
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- Springer Nature
- Number of pages
- 9
- Grant note
- Uehara Memorial Foundation Research Program for Intractable Disease by the Ministry of Health, Labour and Welfare of Japan 16km0405205h0101 / Japan Agency for Medical Research and Development; Japan Agency for Medical Research and Development (AMED) H26-kanenjitsu-kanen-ippan-004 / Ministry of Health, Labour and Welfare of Japan; Ministry of Health, Labour and Welfare, Japan Takeda Science Foundation; Takeda Science Foundation (TSF) 23591006; 26293181; 15K19357; 17K09449; 15K19314; 15K06908 / Japan Society for the Promotion of Science; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Senshin Medical Research Foundation; SENSHIN Medical Research Foundation National Hospital Organization
- Language
- English
- Date published
- 05/23/2018
- Academic Unit
- Gastroenterology and Hepatology; Internal Medicine
- Record Identifier
- 9984359674502771
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