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

Abstract

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 fromAPOA1(rs670) andAPOC3(rs5128) with gout.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).In Polynesians, the T-allele ofrs670(APOA1) increased (odds ratio, OR = 1.53, P = 4.9 × 10(-6)) and the G-allele ofrs5128(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 forrs670(OR = 1.11, P = 0.055), with a significant protective effect of the G-allele forrs5128being observed after adjustment for triglycerides and HDL-C (OR = 0.81, P = 0.039). The effect atrs5128was specific to males in both Europeans and Polynesians. Association in Polynesians was independent of any effect ofrs670andrs5128on triglyceride and HDL-C levels. There was no evidence for association of either single-nucleotide polymorphism with serum urate levels (P ⩾ 0.10).Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout.