ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2276

Pleiotropic Effect of ABCG2 in Gout

Tony R. Merriman1, Amanda Phipps-Green2, James Boocock2, Philip Riches3, Anne-Kathrin Tausche4, Timothy Radstake5, Matthijs Janssen6, Leo .A.B. Joosten7, Tim L Jansen8, Alexander So9, Jennie Harre Hindmarsh10, Lisa K. Stamp11, Nicola Dalbeth12 and Rebekah Wrigley2, 1Biochemistry Dept, PO Box 56, University of Otago, Dunedin, New Zealand, 2University of Otago, Dunedin, New Zealand, 3University of Edinburgh, Edinburgh, United Kingdom, 4Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany, 5Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 6Department of Rheumatology, Rijnstate Hospital Arnhem, Arnhem, Netherlands, 7Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands, 8Rheumatology, Radboud University Medical Center, Nijmegen, Netherlands, 9Rheumatology Department, Lausanne University Hospital, Switzerland, Lausanne, Switzerland, 10Ngati Porou Hauora Charitable Trust, Te Puia Springs, New Zealand, 11University of Otago, Christchurch, New Zealand, 12University of Auckland, Auckland, New Zealand

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: ,

Session Information

Date: Tuesday, November 15, 2016

Title: Metabolic and Crystal Arthropathies - Poster II: Epidemiology and Mechanisms of Disease

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: The ABCG2 Q141K (rs2231142) variant is an established cause of hyperuricaemia in Europeans. Although the effect size of ABCG2 rs2231142 on serum urate levels is ~60% that of SLC2A9, the effect size of ABCG2 on gout is consistently greater than that of SLC2A91,2. We tested the hypothesis that ABCG2 plays a role in gout additional to causing hyperuricemia by testing for association of rs2231142 with gout using asymptomatic hyperuricemic controls. SLC2A9 rs11942223 was included for comparison.

Methods: There were 1,672 European gout cases and 15,367 controls and 1,197 New Zealand Polynesian (Māori and Pacific Island) gout cases and 1,371 controls. The Polynesian sample set was divided into Eastern (EP) and Western Polynesian (WP). Association testing was done using logistic regression with multivariate adjusting for confounding variables, including highest recorded serum urate in analyses with gout cases.

Results: In the European sample set, the 141K allele was strongly associated with asymptomatic hyperuricemia compared with normouricemic controls (OR=1.55, P=4.3×10-18) and with gout compared with asymptomatic hyperuricemia controls (OR=1.83, P=2.6×10-14). In the Polynesian sample sets, the 141K variant was not associated with asymptomatic hyperuricemia compared with normouricemic controls (WP: OR=1.22, P=0.35; EP: OR=0.99, P=0.97) whereas there was a strong risk effect for gout compared with asymptomatic hyperuricemia (WP: OR=2.35, P=3.9×10-5; EP: OR=2.15, P=0.010). For SLC2A9 rs11942223, there was no positive association with gout compared with asymptomatic hyperuricemia controls in any of the ancestral sample sets (Europeans: OR=0.82, P=0.022; WP: OR=0.81, P=0.69 and EP: OR=1.39, P=0.41).

Conclusion: These data are consistent with a role for ABCG2 141K in gout pathogenesis when hyperuricemia is established, potentially through formation of monosodium urate crystals and/or regulation of the inflammatory response to deposited crystals. In Polynesian people ABCG2 141K does not play a role in determining hyperuricemia. 1. Kottgen et al. Nat Genet 2013;45:145-54. 2. Phipps-Green et al. Ann Rheum Dis 2016;75:124-30.

Disclosure: T. R. Merriman, None; A. Phipps-Green, None; J. Boocock, None; P. Riches, None; A. K. Tausche, None; T. Radstake, None; M. Janssen, None; L. A. B. Joosten, None; T. L. Jansen, None; A. So, None; J. Harre Hindmarsh, University of Otago research sub-contract with my employer), 9; L. K. Stamp, None; N. Dalbeth, None; R. Wrigley, None.

To cite this abstract in AMA style:

Merriman TR, Phipps-Green A, Boocock J, Riches P, Tausche AK, Radstake T, Janssen M, Joosten LAB, Jansen TL, So A, Harre Hindmarsh J, Stamp LK, Dalbeth N, Wrigley R. Pleiotropic Effect of ABCG2 in Gout [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/pleiotropic-effect-of-abcg2-in-gout/. Accessed .

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