POGLUT1, the putative effector gene driven by rs2293370 in primary biliary cholangitis susceptibility locus chromosome 3q13.33 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Yuki Hitomi, Kazuko Ueno, Yosuke Kawai, Nao Nishida, Kaname Kojima, Minae Kawashima, Yoshihiro Aiba, Hitomi Nakamura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ohta, Kazuhiro Sugi, Toshiki Nikami, Tsutomu Yamashita, Shinji Katsushima, Toshiki Komeda, Keisuke Ario, Atsushi Naganuma, Masaaki Shimada, Noboru Hirashima, Kaname Yoshizawa, Fujio Makita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Haruhiro Yamashita, Kouki Matsushita, Seiji Tsunematsu, Iwao Yabuuchi, Hideo Nishimura, Yusuke Shimada, Kazuhiko Yamauchi, Tatsuji Komatsu, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Yoko Nakamura, Hiroshi Kamitsukasa, Takeaki Sato, Makoto Nakamuta, Naohiko Masaki, Hajime Takikawa, Atsushi Tanaka, Hiromasa Ohira, Mikio Zeniya, Masanori Abe, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Akinobu Takaki, Satoshi Yamagiwa, Masataka Seike, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Hirotoshi Ebinuma, Takashi Himoto, Kazumoto Murata, Shinji Shimoda, Shinya Nagaoka, Seigo Abiru, Atsumasa Komori, Kiyoshi Migita, Masahiro Ito, Hiroshi Yatsuhashi, Yoshihiko Maehara, Shinji Uemoto, Norihiro Kokudo, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura

ABSTRACT

Primary biliary cholangitis (PBC) is a chronic and cholestatic autoimmune liver disease caused by the destruction of intrahepatic small bile ducts. Our previous genome-wide association study (GWAS) identified six susceptibility loci for PBC. Here, in order to further elucidate the genetic architecture of PBC, a GWAS was performed on an additional independent sample set, then a genome-wide meta-analysis with our previous GWAS was performed based on a whole-genome single nucleotide polymorphism (SNP) imputation analysis of a total of 4,045 Japanese individuals (2,060 cases and 1,985 healthy controls). A susceptibility locus on chromosome 3q13.33 (including ARHGAP31, TMEM39A, POGLUT1, TIMMDC1, and CD80) was previously identified both in the European and Chinese populations and was replicated in the Japanese population (OR = 0.7241, P = 3.5 × 10-9). Subsequent in silico and in vitro functional analyses identified rs2293370, previously reported as the top-hit SNP in this locus in the European population, as the primary functional SNP. Moreover, e-QTL analysis indicated that the effector gene of rs2293370 was Protein O-Glucosyltransferase 1 (POGLUT1) (P = 3.4 × 10-8). This is the first study to demonstrate that POGLUT1 and not CD80 is the effector gene regulated by the primary functional SNP rs2293370, and that increased expression of POGLUT1 might be involved in the pathogenesis of PBC. More... »

PAGES

102

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-36490-1

DOI

http://dx.doi.org/10.1038/s41598-018-36490-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111273932

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30643196


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