摘要目的 探讨CC趋化因子配体2(CCL2)-2518A/G多态性与SLE发病的相关性及其对CCL2表达的影响.方法 本研究纳入134例SLE患者及56名性别年龄匹配的健康体检者作为对照.采用ELISA检测134例SLE患者及56名健康体检者血浆CCL2水平,PCR-限制性片段长度多态性(RFLP)方法检测所有SLE患者及健康体检者CCL2-2518A/G基因型,并采用体外细胞培养方法观察基因型对PBMCs表达CCL2的影响.采用x2检验、t检验,Mann-Whitney U检验进行统计学处理.结果 SLE患者组血浆CCL2表达水平为358.5(500.1) pg/ml [中位数(四分位间距)],高于对照组243.6(125.8) pg/ml(Z=3.892,P=0.000).其中血浆CCL2水平高表达组的SLE患者更易患LN (x2=7.159,P=0.007)、皮肤黏膜损伤(x2=5.133,P=0.023),并具有较高的SLEDAI(Z=2.105,P=0.035).结合研究个体的CCL2-2518A/G多态性基因型分析提示,携带G/G纯合子的SLE患者血浆CCL2水平为425.7(608.8) pg/ml,明显高于G/A杂合子的355.3(511.1) pg/ml及A/A纯合子的327.8(367.9) pg/ml (x2=3.496,P=0.048).体外实验结果显示,携带G/G纯合子的PBMCs经脂多糖刺激后CCL2表达增高较A/A纯合子的PBMCs更为明显(P＜0.05).结论 SLE患者外周血CCL2蛋白水平增高与组织损伤和高SLEDAI相关,表明CCL2可能在SLE的病理过程中起着重要作用.CCL2-2518A/G基因多态性虽与SLE发病无关,但可在炎症环境中通过促进CCL2的表达,从而影响SLE的病情.

abstractsObjective To explore the correlation between chemokine C-C motif ligand 2 (CCL2)-2518A/G polymorphism and the incidence of systemic lupus erythematosus (SLE),and investigate the effects of CCL2-2518A/G polymorphism on the expression of CCL2.Methods A total of 134 SLE patients and 56 sex and age matched healthy people were enrolled in this study.CCL2 plasma levels were measured by enzymelinked immunosorbent assay(ELISA).The 2518 A/G polymorphism in CCL2 promoter region was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP),and then peripheral blood mononuclear cells (PBMCs) were cultured in vitro to explore the influence of the 2518A/G polymorphism in CCL2 promoter region on the expression of CCL2.Mann-Whitney U-test,Student's t test and chi-squared test were used for analysis.Results The plasma CCL2 level in the SLE group was 358.5 (500.1) pg/ml [median (four interval)],which was significantly higher than that in the control group 243.6(125.8) pg/ml (Z=3.892,P=0.000).Patients with high plasma CCL2 levels were more prone to have renal (x2=7.159,P=0.007) and der-matomucosal (x2=5.133,P=0.023) involvement,as well as much higher disease activity index (SLEDAI) scores (Z=2.012,P=0.047).The results of the analysis of individual CCL2-2518A/G polymorphic genotypes suggested that patients with the G/G genotype had the highest CCL2 levels 425.7 (608.8) pg/ml,followed by those with the G/A genotype 355.3(511.1) pg/ml and A/A genotype 327.8(367.9) pg/ml (x2=3.496,P=0.048).The results of in vitro experiment showed that after the stimulation of lipopolysaccharide,the expression of CCL2 in PBMCs with G/G homozygote increased more significantly than that with A/A homozygote (P＜0.05).Conclusion The increase of plasma CCL2 concentrations is associated with tissue injury and high SLEDAI,which suggests that CCL2 may play a crucial role in the pathogenesis of SLE.CCL2-2518A/G polymorphism is not related to the pathogenesis of SLE,but it can affect the condition of SLE by promoting the expression of CCL2 in inflammatory environment.