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. StampNicola Dalbeth, Tony R. Merriman

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)1421-1430
    Number of pages10
    JournalRheumatology (United Kingdom)
    Volume55
    Issue number8
    DOIs
    Publication statusPublished - Aug 2016

    Keywords

    • Apolipoprotein
    • Association
    • Gene
    • Gout
    • Hyperuricaemia

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