Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout

Kawamura, Yusuke; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Okada, Yukinori; Yamamoto, Ken; Higashino, Toshihide; Sakiyama, Masayuki; Shimizu, Toru; Ooyama, Hiroshi; Ooyama, Keiko; Nagase, Mitsuo; Hidaka, Yuji; Shirahama, Yuko; Hosomichi, Kazuyoshi; Nishida, Yuichiro; Shimoshikiryo, Ippei; Hishida, Asahi; Katsuura-Kamano, Sakurako; Shimizu, Seiko; Kawaguchi, Makoto; Uemura, Hirokazu; Ibusuki, Rie; Hara, Megumi; Naito, Mariko; Takao, Mikiya; Nakajima, Mayuko; Iwasawa, Satoko; Nakashima, Hiroshi; Ohnaka, Keizo; Nakamura, Takahiro; Stiburkova, Blanka; Merriman, Tony R; Nakatochi, Masahiro; Ichihara, Sahoko; Yokota, Mitsuhiro; Takada, Tappei; Saitoh, Tatsuya; Kamatani, Yoichiro; Takahashi, Atsushi; Arisawa, Kokichi; Takezaki, Toshiro; Tanaka, Keitaro; Wakai, Kenji; Kubo, Michiaki; Hosoya, Tatsuo; Ichida, Kimiyoshi; Inoue, Ituro; Shinomiya, Nariyoshi; Matsuo, Hirotaka

doi:10.1136/annrheumdis-2019-215521

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ID	114985
著者	Kawamura, Yusuke National Defense Medical College Nakaoka, Hirofumi National Institute of Genetics Nakayama, Akiyoshi National Defense Medical College\|Japan Air Self-Defense Force Okada, Yukinori Osaka University\|RIKEN Center for Integrative Medical Sciences Yamamoto, Ken Kurume University Higashino, Toshihide National Defense Medical College Sakiyama, Masayuki National Defense Medical College Shimizu, Toru Midorigaoka Hospital\|Kyoto Industrial Health Association Ooyama, Hiroshi Ryougoku East Gate Clinic Ooyama, Keiko Ryougoku East Gate Clinic Nagase, Mitsuo Nagase Clinic Hidaka, Yuji Akasaka Central Clinic Shirahama, Yuko Kurume University Hosomichi, Kazuyoshi Kanazawa University Nishida, Yuichiro Saga University Shimoshikiryo, Ippei Kagoshima University Hishida, Asahi Nagoya University (勝浦)釜野, 桜子 The University of Tokushima 徳島大学教育研究者総覧 KAKEN研究者をさがす Shimizu, Seiko National Defense Medical College Kawaguchi, Makoto National Defense Medical College 上村, 浩一 The University of Tokushima KAKEN研究者をさがす Ibusuki, Rie Kagoshima University Hara, Megumi Saga University Naito, Mariko Nagoya University\|Hiroshima University Takao, Mikiya National Defense Medical College Nakajima, Mayuko National Defense Medical College Iwasawa, Satoko National Defense Medical College Nakashima, Hiroshi National Defense Medical College Ohnaka, Keizo Kyushu University Nakamura, Takahiro National Defense Medical College Stiburkova, Blanka Institute of Rheumatology, Prague\|Charles University Merriman, Tony R University of Otago Nakatochi, Masahiro Nagoya University Ichihara, Sahoko Jichi Medical University Yokota, Mitsuhiro Aichi Gakuin University Takada, Tappei The University of Tokyo 齊藤, 達哉 Osaka University\|Tokushima University KAKEN研究者をさがす Kamatani, Yoichiro RIKEN Center for Integrative Medical Sciences\|Kyoto University Takahashi, Atsushi RIKEN Center for Integrative Medical Sciences\|National Cerebral and Cardiovascular Center 有澤, 孝吉 The University of Tokushima 徳島大学教育研究者総覧 KAKEN研究者をさがす Takezaki, Toshiro Kagoshima University Tanaka, Keitaro Saga University Wakai, Kenji Nagoya University Kubo, Michiaki RIKEN Center for Integrative Medical Sciences Hosoya, Tatsuo Jikei University School of Medicine Ichida, Kimiyoshi Jikei University School of Medicine\|Tokyo University of Pharmacy and Life Sciences Inoue, Ituro National Institute of Genetics Shinomiya, Nariyoshi National Defense Medical College Matsuo, Hirotaka National Defense Medical College
資料タイプ	学術雑誌論文
抄録	Objective The first ever genome-wide association study (GWAS) of clinically defined gout cases and asymptomatic hyperuricaemia (AHUA) controls was performed to identify novel gout loci that aggravate AHUA into gout. Methods We carried out a GWAS of 945 clinically defined gout cases and 1003 AHUA controls followed by 2 replication studies. In total, 2860 gout cases and 3149 AHUA controls (all Japanese men) were analysed. We also compared the ORs for each locus in the present GWAS (gout vs AHUA) with those in the previous GWAS (gout vs normouricaemia). Results This new approach enabled us to identify two novel gout loci (rs7927466 of CNTN5 and rs9952962 of MIR302F) and one suggestive locus (rs12980365 of ZNF724) at the genome-wide significance level (p<5.0×10– 8). The present study also identified the loci of ABCG2, ALDH2 and SLC2A9. One of them, rs671 of ALDH2, was identified as a gout locus by GWAS for the first time. Comparing ORs for each locus in the present versus the previous GWAS revealed three ‘gout vs AHUA GWAS’-specific loci (CNTN5, MIR302F and ZNF724) to be clearly associated with mechanisms of gout development which distinctly differ from the known gout risk loci that basically elevate serum uric acid level. Conclusions This meta-analysis is the first to reveal the loci associated with crystal-induced inflammation, the last step in gout development that aggravates AHUA into gout. Our findings should help to elucidate the molecular mechanisms of gout development and assist the prevention of gout attacks in high-risk AHUA individuals.
掲載誌名	Annals of the Rheumatic Diseases
ISSN	00034967 14682060
cat書誌ID	AA00533085 AA12778137
出版者	BMJ Publishing Group
巻	78
号	10
開始ページ	1430
終了ページ	1437
発行日	2019-07-08
権利情報	This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
EDB ID	361068
出版社版DOI	10.1136/annrheumdis-2019-215521
出版社版URL	https://doi.org/10.1136/annrheumdis-2019-215521
フルテキストファイル	annrheumdis_78_10_1430.pdf 2.26 MB
言語	eng
著者版フラグ	出版社版
部局	医学系先端酵素学研究所