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Background and purpose: The proteasome subunit α type 6 (PSMA6) is an important proteolytic protein regulating the expression of genes involved in inflammation. Recently, a functional polymorphism rs1048990, located in PSMA6, has been reported with the susceptibility to ischemic stroke (IS) in several ethnic cohorts, but the results were inconsistent. Moreover, it still lacks the data in Asian. The purpose of the present study was to determine whether this polymorphism confers significant risk to IS in a Chinese population.Methods: A total of 1102 IS cases and 975 healthy controls were analyzed in our study. We genotyped rs1048990 with ligation detection reaction (LDR) method and then performed a meta-analysis.Results: Significant association between rs1048990 in PSMA6 and ischemic stroke was observed in all comparison models (genotype, p=0.016; allele, p=0.004; CG+GG vs. CC, adjusted p=0.006; GG vs. CG+CC, adjusted p=0.038). Further stratification for stroke subtype, similar differences also can be found in large artery atherosclerosis and cardioembolism, but not small vessel occlusion. In addition, in the analysis of genotype-phenotype correlation, the onset ages of allele-G carriers have a trend to be older than non-carriers’ (p<0.001). In the meta-analysis, there is no significant difference between rs1048990 and ischemic stroke, for the great discrepancy of the genotype composition between Caucasian and Chinese.Conclusion: Our study suggests that rs1048990 contributes to the risk of IS and its subtypes in Chinese population, but these associations may vary in different ethnic populations.