Mahmoudi Mahdi, Fallahian Faranak, Sobhani Soheila, Ghoroghi Shima, Jamshidi Ahmadreza, Poursani Shiva, Dolati Masoumeh, Hosseinpour Zahra, Gharibdoost Farhad
Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave,, P.o. box: 1411713137, Tehran, Iran.
Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
Clin Rheumatol. 2017 Apr;36(4):853-862. doi: 10.1007/s10067-016-3526-0. Epub 2017 Jan 24.
Genetic factors have a great role in the pathogenesis of autoimmune diseases by cooperating with environmental stimuli. Killer immunoglobulin-like receptors (KIRs) are cell surface proteins on NK cells whose association with major histocompatibility complex-I regulates their killing function. The aim of this study was to provide information on the possible association between KIR and human leukocyte antigen (HLA) genes with systemic sclerosis disease in Iranian population. A total of 279 systemic sclerosis patients and 451 healthy controls were enrolled in this case-control study in order to determine the presence or absence of 19 KIR genes and 6 specific HLA class I ligands. DNA was analyzed by polymerase chain reaction using the specific sequence primer method (PCR-SSP). Among 11 discovered KIR genotypes, 6 genotypes showed a considerable role and 4 genotypes could preclude the risk of systemic sclerosis (SSc) disease. The gene-gene interactions were also analyzed, and significant confounding effects were seen between involved genes in these two combinations: "KIR3DL1; HLA-BW4-Thr80" and "KIR3DL1 -HLA-BW4-A1." None of single KIR genes showed significant effect on the risk of SSc. We conclude that there is an important relationship between KIR genes and their HLA ligands with incidence rate of systemic sclerosis in Iranian population. The powerful role of a number of discovered KIR/HLA compounds such as activating KIR genotype 3 and HLA-BW4-A1 confirmed the provocative hypothesis of the interplay between activating or inhibitory KIR genes with HLA ligands as a critical index of systemic sclerosis predisposition.
遗传因素通过与环境刺激协同作用，在自身免疫性疾病的发病机制中发挥着重要作用。杀伤细胞免疫球蛋白样受体（KIR）是自然杀伤细胞（NK细胞）表面的蛋白质，其与主要组织相容性复合体-I的关联调节着NK细胞的杀伤功能。本研究的目的是提供有关伊朗人群中KIR基因和人类白细胞抗原（HLA）基因与系统性硬化症之间可能关联的信息。在这项病例对照研究中，共纳入了279例系统性硬化症患者和451名健康对照，以确定19种KIR基因和6种特定HLA-I类配体的存在与否。采用序列特异性引物聚合酶链反应（PCR-SSP）方法对DNA进行分析。在发现的11种KIR基因型中，6种基因型显示出相当大的作用，4种基因型可降低系统性硬化症（SSc）疾病的风险。还分析了基因-基因相互作用，在这两种组合的相关基因之间观察到显著的混杂效应：“KIR3DL1；HLA-BW4-Thr80”和“KIR3DL1 -HLA-BW4-A1”。没有单个KIR基因对SSc风险显示出显著影响。我们得出结论，在伊朗人群中，KIR基因及其HLA配体与系统性硬化症的发病率之间存在重要关系。一些发现的KIR/HLA组合，如激活型KIR基因型3和HLA-BW4-A1的强大作用，证实了激活或抑制性KIR基因与HLA配体之间相互作用的激发性假设，这是系统性硬化症易感性的关键指标。
