ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2099

Genome-Wide Association Study of Clinically-Defined Gout Identifies Multiple Risk Loci: A Clue for Future Companion Diagnostics of Gout

Hirotaka Matsuo1, Ken Yamamoto2, Hirofumi Nakaoka3, Akiyoshi Nakayama1, Masayuki Sakiyama1, Atsushi Takahashi4,5, Takahiro Nakamura6, Yusuke Kawamura1, Nobuyuki Hamajima7, Ituro Inoue8, Michiaki Kubo4, Kimiyoshi Ichida9, Hiroshi Ooyama10, Toru Shimizu11 and Nariyoshi Shinomiya1, 1Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan, 2Department of Medical Chemistry, Kurume University School of Medicine, Kurume, Japan, 3Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Mishima, Japan, 4Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan, 5Research Center, National Cerebral and Cardiovascular Center, Suita, Japan, 6National Defense Medical College, Laboratory for Mathematics, Tokorozawa, Japan, 7Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan, 8Department of Integrated Genetics, National Institute of Genetics, Mishima, Japan, 9Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan, 10Ryougoku East Gate Clinic, Tokyo, Japan, 11Midorigaoka Hospital, Takatsuki, Japan

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , , ,

Session Information

Date: Monday, November 9, 2015

Title: Genetics, Genomics and Proteomics

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Gout, caused by hyperuricaemia, is a multifactorial disease. Recently, genome-wide association studies (GWASs) of gout have been reported; however, they included self-reported gout cases. Therefore, the relationship between genetic variation and clinical subtypes of gout remains to be clarified. We hereby first performed a GWAS of clinically-defined gout cases only.

Methods: A GWAS was conducted with 945 clinically-defined gout cases and 1,213 controls in a Japanese male population. Additionally, a replication study of 1,048 clinically-defined cases and 1,334 controls was performed.

Results: We identified five susceptibility loci for gout at the genome-wide significance level (p≺ 5.0 × 10-8, which contained well-known urate transporter genes (ABCG2 and SLC2A9) and additional genes reported to have relationships with metabolic pathways: rs1260326 (p = 1.9 × 10-12; OR = 1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p = 1.6 × 10-23; OR = 1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus), and rs4073582 (p = 6.4 × 10-9; OR = 1.66) of CNIH-2 (a gene for regulation of glutamate signaling). The latter two are identified as novel loci for gout. Furthermore, we demonstrated that the identified SNPs were differentially associated with types of gout and clinical parameters underlying specific subtypes. The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case-control ORs for two distinct types of gout (r = 0.96 [p = 4.8 × 10-4] for urate clearance and r = 0.96 [p = 5.0 × 10-4] for urinary urate excretion).

Conclusion: Our findings provide clues to better understand the pathogenesis of gout and will be useful to develop companion diagnostics of gout.

Disclosure: H. Matsuo, a patent, 9; K. Yamamoto, None; H. Nakaoka, None; A. Nakayama, None; M. Sakiyama, None; A. Takahashi, None; T. Nakamura, None; Y. Kawamura, None; N. Hamajima, None; I. Inoue, None; M. Kubo, None; K. Ichida, None; H. Ooyama, None; T. Shimizu, None; N. Shinomiya, a patent, 9.

To cite this abstract in AMA style:

Matsuo H, Yamamoto K, Nakaoka H, Nakayama A, Sakiyama M, Takahashi A, Nakamura T, Kawamura Y, Hamajima N, Inoue I, Kubo M, Ichida K, Ooyama H, Shimizu T, Shinomiya N. Genome-Wide Association Study of Clinically-Defined Gout Identifies Multiple Risk Loci: A Clue for Future Companion Diagnostics of Gout [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/genome-wide-association-study-of-clinically-defined-gout-identifies-multiple-risk-loci-a-clue-for-future-companion-diagnostics-of-gout/. Accessed .

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