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Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout
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 c...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788923/ https://www.ncbi.nlm.nih.gov/pubmed/31289104 http://dx.doi.org/10.1136/annrheumdis-2019-215521 |
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author | 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 |
author_facet | 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 |
author_sort | Kawamura, Yusuke |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6788923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-67889232019-10-25 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 Ann Rheum Dis Crystal Arthropathies 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. BMJ Publishing Group 2019-10 2019-07-08 /pmc/articles/PMC6788923/ /pubmed/31289104 http://dx.doi.org/10.1136/annrheumdis-2019-215521 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. 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/. |
spellingShingle | Crystal Arthropathies 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 Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout |
title | Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout |
title_full | Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout |
title_fullStr | Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout |
title_full_unstemmed | Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout |
title_short | Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout |
title_sort | genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout |
topic | Crystal Arthropathies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788923/ https://www.ncbi.nlm.nih.gov/pubmed/31289104 http://dx.doi.org/10.1136/annrheumdis-2019-215521 |
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