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 (ORT allele=1.11, P=0.059; OR=1.01G 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.
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 September 18, 2020.
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