Table_2_Association of CD40 Gene Polymorphisms With Systemic Lupus Erythematosus and Rheumatoid Arthritis in a Chinese Han Population.docx

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune diseases. CD40 participates in inflammatory response, and promotes fibroblast proliferation, leading to occurrence and progression of SLE, RA. This study explores CD40 gene polymorphisms in SLE and RA patients from a Chinese Han population. Two hundred SLE patients, 340 RA patients, and 900 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood, and six polymorphisms of CD40 gene (rs3765456, rs1569723, rs73115010, rs13040307, rs1883832, and rs4810485) were detected by KASP method. Frequencies of rs1569723 genotypes AA, AC, AA+AC were significantly higher in RA patients as compared to those in healthy controls (P = 0.049, P = 0.024, P = 0.022). Frequencies of genotypes CT, CC+CT of rs1883832, and GT, GG+GT of rs4810485 were significantly higher in RA patients as compared to those in healthy controls (P = 0.012, P = 0.018, P = 0.009, P = 0.015). RA patients carrying rs13040307 C allele and rs73115010 T allele showed increased number of swollen joints. Moreover, frequency of allele T of rs13040307 was lower in SLE patients with positive anti-dsDNA and hematuria as compared to that in patients without these parameters (P = 0.038, P = 0.045). There were increased frequencies of genotype TT, allele T for rs13040307 and lower frequencies of genotype TT, allele T for rs73115010 in lupus patients with myositis (all P<0.05). Interestingly, frequencies of rs1569723 A allele, rs4810485 T allele were higher in SLE patients with myositis, and frequencies of rs3765456 A allele, rs1883832 T allele were lower in SLE patients with myositis (All P<0.05). In conclusion, CD40 gene polymorphisms may associate with susceptibility to SLE and RA.

系统性红斑狼疮（systemic lupus erythematosus, SLE）与类风湿关节炎（rheumatoid arthritis, RA）均为复杂的自身免疫性疾病。CD40参与炎症反应，可促进成纤维细胞增殖，进而参与SLE与RA的发生与病情进展。本研究针对中国汉族人群的SLE及RA患者，探讨CD40基因多态性与二者的关联。本研究共纳入200例SLE患者、340例RA患者及900例健康对照者。采集所有受试者外周血提取基因组DNA，采用KASP技术对CD40基因的6个多态位点（rs3765456、rs1569723、rs73115010、rs13040307、rs1883832及rs4810485）进行分型检测。相较于健康对照者，RA患者中rs1569723的AA基因型、AC基因型及AA+AC联合基因型的频率均显著升高（P分别为0.049、0.024、0.022）。RA患者中rs1883832的CT基因型、CC+CT联合基因型，以及rs4810485的GT基因型、GG+GT联合基因型的频率均显著高于健康对照者（P分别为0.012、0.018、0.009、0.015）。携带rs13040307 C等位基因与rs73115010 T等位基因的RA患者，其肿胀关节数量显著增多。此外，合并抗双链DNA（anti-dsDNA）抗体阳性与血尿的SLE患者，其rs13040307的T等位基因频率显著低于无此类异常的SLE患者（P分别为0.038、0.045）。伴肌炎的狼疮患者中，rs13040307的TT基因型与T等位基因频率升高，而rs73115010的TT基因型与T等位基因频率降低，上述差异均具有统计学意义（均P<0.05）。值得注意的是，伴肌炎的SLE患者中，rs1569723的A等位基因与rs4810485的T等位基因频率升高，而rs3765456的A等位基因与rs1883832的T等位基因频率降低，所有差异均具有统计学意义（均P<0.05）。综上，CD40基因多态性可能与SLE及RA的易感性相关。