The level of chemokine C-C motif ligand 2 in systemic lupus erythematosus patients and its association with the 2518 A/G polymorphism in the CCL2 promoter region / 中华风湿病学杂志

ABSTRACT

Objective 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.