Objective To explore the association of CD40 gene single nucleotide polymorphisms (SNPs) and haplotypes with the susceptibility to systemic lupus erythematosus (SLE),as well as the association of serum levels and genotypes of CD40 with the occurrence of SLE.Methods A multiplex PCR single-base extension assay (PCR-SBE) and DNA sequencing were performed to analyze 4 SNPs of the CD40 gene,including rs1883832 C/T,rs13040307 C/T,rs752118 C/T and rs3765459 G/A,in 205 patients with SLE (SLE group) and 220 healthy human controls (control group).Enzyme-linked immunosorbent assay (ELISA) was conducted to measure serum levels of CD40 in these subjects.Results Compared with the control group,the SLE group showed significantly increased serum levels of CD40 (P ＜ 0.05).There were significant differences in genotype and allele frequencies of the SNP rs1883832 C/T in the CD40 gene between the SLE group and control group (all P＜ 0.01).Relative risk analysis showed that the risk of developing SLE in rs1883832 T allele carriers was 1.517 times that in rs1883832 C allele carriers (OR =1.517,95％ CI:1.157-1.990,P=0.003).Moreover,serum levels of CD40 were significantly higher in rs1883832 T allele carriers than in rs1883832 C allele carriers (P ＜ 0.01).The risk of developing SLE was significantly increased in TCCA haplotype carriers compared with the healthy controls (OR =2.322,95％ CI:1.181-4.564,P=0.012).Conclusion The CD40 gene rs1883832 C/T polymorphism and its TCCA haplotype were both associated with the occurrence of SLE,and the rs1883832 T allele may be a gene predisposing to SLE.