Gout is an auto-inflammatory arthritis caused by deposition of crystallized monosodium urate (MSU) in and around joints in the presence of hyperuricemia. However, there are other factors that control progression from hyperuricemia to gout. Alpha-1 antitrypsin (AAT; alpha1-proteinase inhibitor encoded by SERPINA1), is an abundant hepatic acute phase protein in humans. In response to inflammation AAT levels increase dramatically in blood. Reduced inflammation in an animal model of gout has been observed when injected with alpha-1-anti-trypsin-IgG1-Fc. Moreover, previous GWAS studies in Japanese and Swiss cohorts reported a significant correlation between SERPINA1 polymorphisms and AAT levels. The aim of our study was to test for association of SERPINA1 polymorphisms (rs12884390,rs28929474,rs11621961,rs4905197) with gout in European and Polynesian groups. A total of 6268 clinically-ascertained gout cases and 14459 controls of various populations of European ancestry (NZ Caucasian, ARIC, FHS, CARDIA, CHS, UK Biobank) and New Zealand Māori and Pacific (Polynesian) ancestry were utilised. Taqman® genotyping was carried out, followed by multivariate-adjusted (age, sex and self-reported grand-parental ancestry in Polynesian) association analysis in R 3.2.2 with gout as the outcome. The T-allele of SERPINA1;rs12884390 exhibited significant association with gout risk in European (OR=0.912,POR=4.01×10-04 ***). However, a non-significant association of the rs12884390 T-allele was found with gout in NZ Polynesian (OR= 0.907, POR=0.183). The minor T-allele of the rs11621961 also conferred a nominal association with gout in Polynesian (OR= 0.872, POR=0.056). This suggests a potential role for the SERPINA1 gene in the inflammatory process that leads to the development of gout.