CD40基因多态性及血清水平与系统性红斑狼疮发病机制的相关研究

目的 探讨CD40基因单核苷酸多态性（SNP）及其单倍型与SLE易感性的相关性，分析CD40基因型及血清水平与系统性红斑狼疮（SLE）的相关性。 方法 单碱基延伸的PCR技术（PCR-SBE）和DNA测序法分析205例SLE患者和220例健康对照CD40基因rs1883832 C/T、 rs13040307 C/T、rs752118 C/T 和rs3765459 G/A的多态性，同时用ELISA检测血清CD40水平。 结果 与健康对照组相比，SLE组血清CD40水平显著增高（P < 0.05）。SLE组与健康对照组CD40基因rs1883832 C/T位点基因型和等位基因频率比较，差异有统计学意义（P < 0.01）。等位基因频率的相对风险分析后发现，携带有rs1883832 T等位基因的受试者患有SLE的风险是rs1883832 C等位基因的1.517倍（OR = 1.517，95% CI 1.157 ~ 1.990，P = 0.003）；携带rs1883832 T等位基因的SLE患者血清CD40水平与不携带者相比，结果显著增高（P < 0.01）。通过联合基因型分析发现，SLE组中携带单倍型TCCA的患者较健康对照组显著增加了发病的风险（OR = 2.322，95% CI 1.181 ~ 4.564，P = 0.012）。 结论 CD40基因rs1883832 C/T多态性和TCCA单倍型与SLE的发病有相关性，其中rs1883832 T等位基因可能是SLE的遗传易感基因。

Association of CD40 gene polymorphisms and serum CD40 levels with the pathogenesis of systemic lupus erythematosus

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.