The proteasome system is a proteolytic pathway that regulates the expression of genes involved in inflammation. Polymorphisms in the gene encoding subunit alpha type 6 (PSMA6)--in particular the rs1048990 exon 1-8C/G SNP--have been implicated with susceptibility to myocardial infarction (MI) in a Japanese study. We examined whether several polymorphisms in the PSMA6 gene were related to MI risk in 6946 nonfatal MI cases and 2720 unrelated controls in a UK population. The homozygous GG genotype for rs1048990 was much less frequent in this UK population than in the Japanese population (2.1 vs 8.9%), and was associated with an odds ratio (OR) for MI of 1.09 (95% confidence interval (CI): 0.98-1.21) per G allele in a co-dominant genetic model and 1.32 (95% CI: 0.90-1.93) in a recessive genetic model. Although not statistically significant, these results for this variant are still consistent with the Japanese hypothesis-generating study. Our findings, when taken together with four other studies (including the hypothesis-generating one), yielded a combined OR for MI of 1.15 (95% CI: 1.08-1.21) per G allele in a co-dominant model and 1.38 (95% CI: 1.22-1.57) for the GG genotype in a recessive model. Larger studies involving more than 10,000 disease cases would be required to further elucidate the role of this variant for susceptibility to MI. However, given the rarity of this variant in Caucasians, the attributable risk of rs1048990 for MI is unlikely to be great in western populations.