number of access : ?
number of downloads : ?
ID 114985
Author
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
Shimizu, Seiko National Defense Medical College
Kawaguchi, Makoto National Defense Medical College
Uemura, Hirokazu The University of Tokushima KAKEN Search Researchers
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
Saitoh, Tatsuya Osaka University|Tokushima University KAKEN Search Researchers
Kamatani, Yoichiro RIKEN Center for Integrative Medical Sciences|Kyoto University
Takahashi, Atsushi RIKEN Center for Integrative Medical Sciences|National Cerebral and Cardiovascular Center
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
Content Type
Journal Article
Description
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.
Journal Title
Annals of the Rheumatic Diseases
ISSN
00034967
14682060
NCID
AA00533085
AA12778137
Publisher
BMJ Publishing Group
Volume
78
Issue
10
Start Page
1430
End Page
1437
Published Date
2019-07-08
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Medical Sciences
Institute of Advanced Medical Sciences