Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with unclear etiology. Several loci associated with genetic susceptibility for lupus have been described. However, it lacks reports on cytokine gene-gene interactions among SLE patients from Asian population. Epistasis interaction among single nucleotide polymorphisms (SNPs) of cytokine genes in Indian SLE patients was tested using multifactor-dimensionality reduction (MDR) analysis. A total of fourteen SNPs lacking linkage disequilibrium among different cytokines genes were genotyped in a cohort of 200 SLE patients and 201 healthy individuals as controls of Indian origin. A high degree of synergism among Lymphotoxin-α (LT-α), Interleukin-1β (IL-1β) and Interleukin-10 (IL-10) gene polymorphisms was detected in our SLE patients. Furthermore, by virtue of biological inter-relations among different cytokines, a high strength of interactions was observed among pro-inflammatory (IL-1β, IL-6) and anti-inflammatory (IL-10) cytokine gene SNPs. Also, among studied pro-inflammatory cytokines and chemokines, a strong synergistic effect among Tumor Necrosis Factor-α (TNF-α), LT-α and Monocyte Chemo-attractant Protein-1 (MCP-1) SNPs was occurred. A nature of strong interaction among the candidate cytokine genes may speculate a proactive role in causing genetic susceptibility to the disease in SLE patients with Indian origin.

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细胞因子基因多位点分析揭示了对印度 SLE 遗传易感性的协同影响——一种多因素降维方法

系统性红斑狼疮（SLE）是一种原型自身免疫性疾病，病因不明。已经描述了几个与狼疮遗传易感性相关的位点。然而，缺乏关于亚洲人群 SLE 患者细胞因子基因-基因相互作用的报道。使用多因素降维 (MDR) 分析测试了印度 SLE 患者细胞因子基因的单核苷酸多态性 (SNP) 之间的上位性相互作用。在 200 名 SLE 患者和 201 名健康个体的队列中，共有 14 个在不同细胞因子基因之间缺乏连锁不平衡的 SNP 被基因分型，作为印度血统的对照。在我们的 SLE 患者中检测到淋巴毒素-α (LT-α)、白介素-1β (IL-1β) 和白介素-10 (IL-10) 基因多态性之间的高度协同作用。此外，由于不同细胞因子之间的生物学相互关系，在促炎 (IL-1β、IL-6) 和抗炎 (IL-10) 细胞因子基因 SNP 之间观察到高强度的相互作用。此外，在研究的促炎细胞因子和趋化因子中，肿瘤坏死因子-α (TNF-α)、LT-α 和单核细胞趋化蛋白-1 (MCP-1) SNP 之间发生了强烈的协同作用。候选细胞因子基因之间强相互作用的性质可能推测在印度血统的 SLE 患者中引起对该疾病的遗传易感性的积极作用。肿瘤坏死因子-α (TNF-α)、LT-α 和单核细胞化学引诱蛋白-1 (MCP-1) SNP 之间发生了强烈的协同作用。候选细胞因子基因之间强相互作用的性质可能推测在印度血统的 SLE 患者中引起对该疾病的遗传易感性的积极作用。肿瘤坏死因子-α (TNF-α)、LT-α 和单核细胞化学引诱蛋白-1 (MCP-1) SNP 之间发生了强烈的协同作用。候选细胞因子基因之间强相互作用的性质可能推测在印度血统的 SLE 患者中引起对该疾病的遗传易感性的积极作用。