A previously detected association between gout and the APOA1–APOC3–APOA4 gene cluster has been confirmed in a larger study, suggesting a causal role. Data from 5,367 Atherosclerosis Risk in Communities and 2,984 Framingham Heart Study participants were compared with findings from a New Zealand cohort of European and Polynesian (Māori and Pacific) individuals, comprising 2,452 healthy controls and 2,690 patients with clinical gout. In Polynesians, the rs670 T allele of APOA1 increased the risk of gout in both sexes (OR 1.53, P = 4.9 × 10−6), whereas the rs5128 G allele of APOC3 decreased the risk of gout in men only (OR 0.86, P = 0.026). Similarly, in Europeans, the rs670 T allele tended to increase gout risk in both sexes, and the rs5128 G allele did decrease gout risk in men; however, the rs5128 effect was only seen after adjustment for triglyceride and HDL-cholesterol levels (OR 0.81, P = 0.039).