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

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

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11 Citations (Scopus)

Abstract

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 â € 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.

Original languageEnglish
Pages (from-to)1430-1437
Number of pages8
JournalAnnals of the Rheumatic Diseases
Volume78
Issue number10
DOIs
Publication statusPublished - Oct 1 2019

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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    Kawamura, Y., Nakaoka, H., Nakayama, A., Okada, Y., Yamamoto, K., Higashino, T., Sakiyama, M., Shimizu, T., Ooyama, H., Ooyama, K., Nagase, M., Hidaka, Y., Shirahama, Y., Hosomichi, K., Nishida, Y., Shimoshikiryo, I., Hishida, A., Katsuura-Kamano, S., Shimizu, S., ... Matsuo, H. (2019). Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout. Annals of the Rheumatic Diseases, 78(10), 1430-1437. https://doi.org/10.1136/annrheumdis-2019-215521