Umare Vinod D, Pradhan Vandana D, Rajadhyaksha Anjali G, Ghosh Kanjaksha, Nadkarni Anita H
National Institute of Immunohaematology, Indian Council of Medical Research, Mumbai, Maharashtra 400012, India.
Department of Rheumatology, King Edward Memorial Hospital, Parel, Mumbai, Maharashtra 400012, India.
Cytokine. 2017 Aug;96:189-194. doi: 10.1016/j.cyto.2017.04.016. Epub 2017 Apr 21.
Systemic Lupus Erythematosus (SLE) is a clinically heterogeneous chronic, inflammatory autoimmune disorder that affects multiple organs where exact etiology of the disease is not yet clearly understood. Various evidences suggest that genetic polymorphisms in inflammatory mediators like cytokines and chemokines may influence development of the disease. Here, we investigated whether functional polymorphism at the Monocyte Chemoattractant Protein-1 (MCP-1) regulatory region associates with disease phenotype in Indian SLE patients. This case control study included 200 SLE patients and 201 ethnically matched healthy controls. Genotyping of MCP-1 (-2518 A/G) polymorphism was performed using PCR-RFLP method. Serum MCP-1 levels were detected by bead-based multiplex immunoassay. Serum MCP-1 levels were found to be higher in patients compared with healthy individuals (p<0.0001). A significant difference for MCP-1G allele frequency (OR=1.9, 95%CI=1.4-2.6, p<0.0001) was observed among SLE patients against healthy individuals. A significant difference in the distribution of MCP-1 -2518GG (OR=3.0, 95%CI=1.4-6.7, p=0.0041) and AG+GG genotypes (OR=2.0, 95%CI=1.4-3.0, p=0.0005) was also noted among SLE patients when compared with healthy individuals. A significant association was observed between A/G and G/G versus A/A genotypes with renal manifestations (p<0.0001, Pc<0.001). Serum MCP-1 levels in active LN patients were found to be significantly higher than inactive LN (p=0.0059), mild LN (p=0.0061) as well as non-LN patients (p=0.0001). These findings suggest that -2518G allele of MCP-1 -2518 A/G polymorphism is associated with renal disorders and may influence MCP-1 gene expression among Indian SLE patients.
系统性红斑狼疮(SLE)是一种临床异质性的慢性炎症性自身免疫性疾病,可累及多个器官,其确切病因尚不清楚。各种证据表明,细胞因子和趋化因子等炎症介质中的基因多态性可能影响该疾病的发展。在此,我们研究了单核细胞趋化蛋白-1(MCP-1)调控区域的功能多态性是否与印度SLE患者的疾病表型相关。这项病例对照研究纳入了200例SLE患者和201例种族匹配的健康对照。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对MCP-1(-2518 A/G)多态性进行基因分型。通过基于微珠的多重免疫测定法检测血清MCP-1水平。发现患者的血清MCP-1水平高于健康个体(p<0.0001)。在SLE患者与健康个体之间观察到MCP-1 G等位基因频率存在显著差异(OR=1.9,95%CI=1.4-2.6,p<0.0001)。与健康个体相比,SLE患者中MCP-1 -2518GG(OR=3.0,95%CI=1.4-6.7,p=0.0041)和AG+GG基因型(OR=2.0,95%CI=1.4-3.0,p=0.0005)的分布也存在显著差异。在A/G和G/G与A/A基因型之间观察到与肾脏表现存在显著关联(p<0.0001,Pc<0.001)。发现活动性狼疮性肾炎(LN)患者的血清MCP-1水平显著高于非活动性LN患者(p=0.0059)、轻度LN患者(p=0.0061)以及非LN患者(p=0.0001)。这些发现表明,MCP-1 -2518 A/G多态性的-2518G等位基因与肾脏疾病相关,并且可能影响印度SLE患者的MCP-1基因表达。