Kawashima Minae, Hitomi Yuki, Aiba Yoshihiro, Nishida Nao, Kojima Kaname, Kawai Yosuke, Nakamura Hitomi, Tanaka Atsushi, Zeniya Mikio, Hashimoto Etsuko, Ohira Hiromasa, Yamamoto Kazuhide, Abe Masanori, Nakao Kazuhiko, Yamagiwa Satoshi, Kaneko Shuichi, Honda Masao, Umemura Takeji, Ichida Takafumi, Seike Masataka, Sakisaka Shotaro, Harada Masaru, Yokosuka Osamu, Ueno Yoshiyuki, Senju Michio, Kanda Tatsuo, Shibata Hidetaka, Himoto Takashi, Murata Kazumoto, Miyake Yasuhiro, Ebinuma Hirotoshi, Taniai Makiko, Joshita Satoru, Nikami Toshiki, Ota Hajime, Kouno Hiroshi, Kouno Hirotaka, Nakamuta Makoto, Fukushima Nobuyoshi, Kohjima Motoyuki, Komatsu Tatsuji, Komeda Toshiki, Ohara Yukio, Muro Toyokichi, Yamashita Tsutomu, Yoshizawa Kaname, Nakamura Yoko, Shimada Masaaki, Hirashima Noboru, Sugi Kazuhiro, Ario Keisuke, Takesaki Eiichi, Naganuma Atsushi, Mano Hiroshi, Yamashita Haruhiro, Matsushita Kouki, Yamauchi Kazuhiko, Makita Fujio, Nishimura Hideo, Furuta Kiyoshi, Takahashi Naohiro, Kikuchi Masahiro, Masaki Naohiko, Tanaka Tomohiro, Tamura Sumito, Mori Akira, Yagi Shintaro, Shirabe Ken, Komori Atsumasa, Migita Kiyoshi, Ito Masahiro, Nagaoka Shinya, Abiru Seigo, Yatsuhashi Hiroshi, Yasunami Michio, Shimoda Shinji, Harada Kenichi, Egawa Hiroto, Maehara Yoshihiko, Uemoto Shinji, Kokudo Norihiro, Takikawa Hajime, Ishibashi Hiromi, Chayama Kazuaki, Mizokami Masashi, Nagasaki Masao, Tokunaga Katsushi, Nakamura Minoru
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Omura, Japan.
Hum Mol Genet. 2017 Feb 1;26(3):650-659. doi: 10.1093/hmg/ddw406.
A previous genome-wide association study (GWAS) performed in 963 Japanese individuals (487 primary biliary cholangitis [PBC] cases and 476 healthy controls) identified TNFSF15 (rs4979462) and POU2AF1 (rs4938534) as strong susceptibility loci for PBC. In this study, we performed GWAS in additional 1,923 Japanese individuals (894 PBC cases and 1,029 healthy controls), and combined the results with the previous data. This GWAS, together with a subsequent replication study in an independent set of 7,024 Japanese individuals (512 PBC cases and 6,512 healthy controls), identified PRKCB (rs7404928) as a novel susceptibility locus for PBC (odds ratio [OR] = 1.26, P = 4.13 × 10-9). Furthermore, a primary functional variant of PRKCB (rs35015313) was identified by genotype imputation using a phased panel of 1,070 Japanese individuals from a prospective, general population cohort study and subsequent in vitro functional analyses. These results may lead to improved understanding of the disease pathways involved in PBC, forming a basis for prevention of PBC and development of novel therapeutics.
此前在963名日本个体（487例原发性胆汁性胆管炎[PBC]患者和476名健康对照）中开展的一项全基因组关联研究（GWAS）确定TNFSF15（rs4979462）和POU2AF1（rs4938534）为PBC的强易感基因座。在本研究中，我们对另外1923名日本个体（894例PBC患者和1029名健康对照）进行了GWAS，并将结果与先前的数据相结合。这项GWAS以及随后在一组独立的7024名日本个体（512例PBC患者和6512名健康对照）中开展的重复研究，确定PRKCB（rs7404928）为PBC的一个新的易感基因座（优势比[OR]=1.26，P=4.13×10−9）。此外,通过对来自一项前瞻性普通人群队列研究的1070名日本个体的分型面板进行基因型推算以及随后的体外功能分析，确定了PRKCB的一个主要功能变异体（rs35015313）。这些结果可能有助于加深对PBC相关疾病途径的理解，为PBC的预防和新型疗法的开发奠定基础。
