Journal Article

Replication of association of the apolipoprotein A1-C3-A4 gene cluster with the risk of gout

Humaira Rasheed, Amanda J. Phipps-Green, Ruth Topless, Malcolm D. Smith, Catherine Hill, Susan Lester, Maureen Rischmueller, Matthijs Janssen, Timothy L. Jansen, Leo A. Joosten, Timothy R. Radstake, Philip L. Riches, Anne-Kathrin Tausche, Frederic Lioté, Alexander So, Andre van Rij, Gregory T. Jones, Sally P. McCormick, Andrew A. Harrison, Lisa K. Stamp, Nicola Dalbeth and Tony R. Merriman

in Rheumatology

Volume 55, issue 8, pages 1421-1430
Published in print August 2016 | ISSN: 1462-0324
Published online April 2016 | e-ISSN: 1462-0332 | DOI: https://dx.doi.org/10.1093/rheumatology/kew057
Replication of association of the apolipoprotein A1-C3-A4 gene cluster with the risk of gout

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  • Rheumatology
  • Immunology
  • Clinical Genetics

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Objective. Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout.

Methods. We studied data for 2452 controls and 2690 clinically ascertained gout cases of European and New Zealand Polynesian (Māori and Pacific) ancestry. Data were also used from the publicly available Atherosclerosis Risk in Communities study (n = 5367) and the Framingham Heart Study (n = 2984). Multivariate adjusted logistic and linear regression was used to test the association of single-nucleotide polymorphisms with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C).

Results. In Polynesians, the T-allele of rs670 (APOA1) increased (odds ratio, OR = 1.53, P = 4.9 × 10−6) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR = 0.86, P = 0.026). In Europeans, there was a strong trend to a risk effect of the T-allele for rs670 (OR = 1.11, P = 0.055), with a significant protective effect of the G-allele for rs5128 being observed after adjustment for triglycerides and HDL-C (OR = 0.81, P = 0.039). The effect at rs5128 was specific to males in both Europeans and Polynesians. 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 single-nucleotide polymorphism with serum urate levels (P ⩾ 0.10).

Conclusion. Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout.

Keywords: gout; hyperuricaemia; gene; association; apolipoprotein

Journal Article.  5994 words.  Illustrated.

Subjects: Rheumatology ; Immunology ; Clinical Genetics

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