Association of the Apolipoprotein A1-C3-A4 Gene Cluster with the Risk of Gout: Evidence for a Causal Role in Gout

Tony R. Merriman¹, Amanda Phipps-Green², Ruth Topless², Malcolm D. Smith³, Catherine Hill⁴, Susan Lester⁴, Maureen Rischmueller⁵, Matthijs Janssen⁶, Tim Jansen⁷, Leo A. Joosten⁸, Timothy Radstake⁹, Philip L. Riches¹⁰, Anne-Kathrin Tausche¹¹, Frederic Lioté¹², Alex So^13,14, Andre M. van Rij², Gregory T. Jones¹⁵, Sally McCormick¹⁶, Andrew Harrison², Lisa K. Stamp¹⁷, Nicola Dalbeth¹⁸ and Humaira Rasheed¹⁶, ¹Biochemistry Dept, PO Box 56, University of Otago, Dunedin, New Zealand, ²University of Otago, Dunedin, New Zealand, ³Rheumatology, Repatriation General Hospital, Adelaide, Australia, ⁴Rheumatology Unit, The Queen Elizabeth Hospital, Woodville, Australia, ⁵Rheumatology, Queen Elizabeth Hospital, Adelaide, Australia, ⁶Rheumatology Dept, Ziekenhuis Rijnstate, Arnhem, Netherlands, ⁷P O Box 581, Haarlem, Netherlands, ⁸Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ⁹Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ¹⁰Centre for Genomic and Experimental Medicine, Western General Hospital, Edinburgh, United Kingdom, ¹¹Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany, ¹²Rheumatology Department; Inserm UMR-S606; Paris-Diderot University, hôpital Lariboisiere, Paris, France, ¹³Service De Rhumatologie, CHUV, Lausanne, Switzerland, ¹⁴Department of Rheumatology, CHUV, Lausanne, Switzerland, ¹⁵Surgery, University of Otago, Dunedin, New Zealand, ¹⁶Department of Biochemistry, University of Otago, Dunedin, New Zealand, ¹⁷Medicine, University of Otago, Christchurch, Christchurch, New Zealand, ¹⁸Department of Medicine, University of Auckland, Auckland, New Zealand

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: gout, risk and uric acid

Session Information

Date: Tuesday, November 10, 2015

Title: Metabolic and Crystal Arthropathies II: Mechanisms and Associations

Session Type: ACR Concurrent Abstract Session

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

Background/Purpose: Gout is caused by an inflammatory response to monosodium urate (MSU) crystals and is associated with elevated triglyceride and very low density lipoprotein levels. There is evidence that suggests apolipoprotein coating of MSU crytsals modulates the inflammatory response. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported. To investigate a possible causal role for this locus in gout we tested the association of genetic variants from APOA1 and APOC3 with gout.

Methods: Testing of rs670 (APOA1) and rs5128 (APOC3) was undertaken in 2452 controls and 2690 clinically-ascertained gout cases of European and of New Zealand Polynesian (Māori and Pacific) ancestry. Data from the publically-available Atherosclerosis Risk in Communities (n=5367) study and the Framingham Heart Study (n=2984) were also analyzed. Multivariate adjusted logistic and linear regression was used to test the association of SNPs with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C).

Results: In Europeans and Polynesians, consistent with previous studies, both SNPs were associated with HDL-C (P≤0.027) and rs5128 was associated with triglyceride levels (P≤0.006). There was no evidence for association of rs670 or rs5128 with the risk of gout in Europeans (OR_{T allele}=1.11, P=0.059; OR=1.01_{G allele}, P=0.91 respectively). In contrast, in Polynesians the T-allele of rs670 (APOA1) increased the risk of gout (OR=1.53, P=4.88×10^-6) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR=0.86, P=0.026). Association in Polynesians was independent of any effect of rs670 and rs5128 on triglyceride and HDL-C levels. There was no evidence for association of either SNP with serum urate levels in Europeans or Polynesians (P≥0.10).

Conclusion: The data supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in the inflammatory response in gout. The effect was specific to Polynesians in this study and could indicate a pathogenic process, outside of the inherent hyperuricaemia present in Polynesians, that contributes to the increased prevalence of gout in this population group.

Disclosure: T. R. Merriman, None; A. Phipps-Green, None; R. Topless, None; M. D. Smith, None; C. Hill, None; S. Lester, None; M. Rischmueller, None; M. Janssen, None; T. Jansen, None; L. A. Joosten, None; T. Radstake, None; P. L. Riches, Menarini, 2; A. K. Tausche, None; F. Lioté, None; A. So, None; A. M. van Rij, None; G. T. Jones, None; S. McCormick, None; A. Harrison, None; L. K. Stamp, None; N. Dalbeth, None; H. Rasheed, None.

To cite this abstract in AMA style:

Merriman TR, Phipps-Green A, Topless R, Smith MD, Hill C, Lester S, Rischmueller M, Janssen M, Jansen T, Joosten LA, Radstake T, Riches PL, Tausche AK, Lioté F, So A, van Rij AM, Jones GT, McCormick S, Harrison A, Stamp LK, Dalbeth N, Rasheed H. Association of the Apolipoprotein A1-C3-A4 Gene Cluster with the Risk of Gout: Evidence for a Causal Role in Gout [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/association-of-the-apolipoprotein-a1-c3-a4-gene-cluster-with-the-risk-of-gout-evidence-for-a-causal-role-in-gout/. Accessed .

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