ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 1630

Genetic Variants of Serum Uric Acid and Gout: An Analysis of > 170,000 Individuals

Hyon Choi1, Robert M. Plenge2, Anna Köttgen3, Veronique Vitart4, Murielle Bochud5, Christian Gieger6, Mark Caulfield7, Marina Ciullo8, Eva Albrecht6, Alexander Teumer9, Gary Curhan10, Jan Krumsiek11, Conall O'Seaghdha12, Caroline Fox13 and The Global Urate Genetics Consortium (GUGC)14, 1Section of Rheumatology and the Clinical Epidemiology Unit, Boston University School of Medicine, Boston, MA, 2Division of Rheumatology, Immunology and Allergy and Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 3Renal Division, Freiburg University Hospital, Freiburg, Germany, 4Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom, 5Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Switzerland, 6German Research Center for Environmental Health, Neuherberg, Germany, 7William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom, 8Institute of Genetics and Biophysics, "A. Buzzati-Traverso", Italy, 9Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt- University Greifswald, Greifswald, Germany, 10German Research Center for Environmental Health, Harvard Medical School, Boston, MA, 11Institute of Bioinformatics and Systems Biology, German Research Center for Environmental Health, Neuherberg, Germany, 12German Research Center for Environmental Health, NHLBI's Framingham Heart Study and Center for Population Studies,, Neuherberg, 13Institute of Genetics and Biophysics, NHLBI's Framingham Heart Study and Center for Population Studies, Framingham, MA, 14Section of Rheumatology and the Clinical Epidemiology Unit, Boston University of School of Medicine, Boston, MA

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: genomics, Gout and uric acid

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Title: Metabolic and Crystal Arthropathies: Basic Science

Session Type: Abstract Submissions (ACR)

Background/Purpose:  Gout is a common and excruciatingly painful inflammatory arthritis caused by hyperuricemia.  In addition to various lifestyle risk factors, a substantial genetic predisposition to gout has long been recognized.  The Global Urate Genetics Consortium (GUGC) has aimed to comprehensively investigate the genetics of serum uric acid and gout using data from > 140,000 individuals of European-ancestry, 8,340 individuals of Indian ancestry, 5,820 African-Americans, and 15,286 Japanese.

Methods:   We performed discovery GWAS meta-analyses of serum urate levels (n=110,347 individuals) followed by replication analyses (n=32,813 different individuals).  Our gout analysis involved 3,151 cases and 68,350 controls, including 1,036 incident gout cases that met the American College of Rheumatology Criteria.  We also examined the association of gout with fractional excretion of uric acid (n=6,799).  A weighted genetic urate score was constructed based on the number of risk alleles across urate-associated loci, and their association with the risk of gout was evaluated.  Furthermore, we examined implicated transcript expression in cis (expression quantitative trait loci databases) for potential insights into the gene underlying the association signal.  Finally, in order to further identify urate-associated genomic regions, we performed functional network analyses that incorporated prior knowledge on molecular interactions in which the gene products of implicated genes operate.

Results: We identified and replicated 28 genome-wide significant loci in association with serum urate (P ≤ 5×10-8), including all previously-reported loci as well as 18 novel genetic loci.  Unlike the majority of previously-identified loci, none of the novel loci appeared to be obvious candidates for urate transport.  Rather, they were mapped to genes that encode for purine production, transcription, or growth factors with broad downstream responses.  Besides SLC2A9 and ABCG2, no additional regions contained SNPs that differed significantly (P < 5x10-8) between sexes.  Urate-increasing alleles were associated with an increased risk of gout for all loci.  The urate genetic risk score (ranging from 10 to 45) was significantly associated with an increased odds of prevalent gout (OR per unit increase, 1.11; 95% CI, 1.09-1.14) and incident gout (OR, 1.10; 95% CI, 1.08-1.13).  Associations for many of the loci were of similar magnitude in individuals of non-European ancestry.  Detailed characterization of the loci revealed associations with transcript expression and the fractional excretion of urate.  Network analyses implicated the inhibins-activins signaling pathways and glucose metabolism in systemic urate control.

Conclusion:   The novel genetic candidates identified in this urate/gout consortium study, the largest to date, highlight the importance of metabolic control of urate production and urate excretion.  The modulation by signaling processes that influence metabolic pathways such as glycolysis and the pentose phosphate pathway appear to be central mechanisms underpinned by the novel GWAS candidates.  These findings may have implications for further research into urate-lowering drugs to treat and prevent gout.


Disclosure:

H. Choi,
None;

R. M. Plenge,
None;

A. Köttgen,
None;

V. Vitart,
None;

M. Bochud,
None;

C. Gieger,
None;

M. Caulfield,
None;

M. Ciullo,
None;

E. Albrecht,
None;

A. Teumer,
None;

G. Curhan,
None;

J. Krumsiek,
None;

C. O’Seaghdha,
None;

C. Fox,
None;

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/genetic-variants-of-serum-uric-acid-and-gout-an-analysis-of-170000-individuals/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology