The aim of this study was to determine whether the functional mannose-binding lectin (MBL2) exon 1 codon 54 polymorphism (rs1800450) confers susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. A meta-analysis was conducted on the MBL2 codon 54 polymorphism across 21 comparative studies. Meta-analysis showed an association between the MBL2 codon 54 B allele and SLE in all study subjects [odds ratio (OR)=1.298, 95% confidence interval (CI)=1.154-1.459, P=1.4×10(-5)]. Analysis after stratification by ethnicity indicated that the MBL2 codon 54 B allele is significantly associated with SLE in Europeans, Asian, and Africans (OR=1.246, 95% CI=1.062-1.462, P=0.007; OR=1.268, 95% CI=1.049-1.532, P=0.014; OR=1.939, 95% CI=1.269-2.962, P=0.002, respectively). However, African Americans had a much lower prevalence of the T allele (5.8%) than any other populations studied, whereas Asians had the highest prevalence (16.2%). This meta-analysis confirms that the MBL2 codon 54 polymorphism is associated with SLE susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent.