Functional and prognostic relevance of the-173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis
Functional and prognostic relevance of the-173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis
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DOI：
10.1002/art.10882
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发表时间：
2003-05-01
影响因子：
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通讯作者：
Martini, A
中科院分区：
文献类型：
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作者：
De Benedetti, F;Meazza, C;Martini, A
目的：通过评估巨噬细胞移动抑制因子（MIF）基因 -173单核苷酸G - C多态性与MIF血清及滑液水平、糖皮质激素需求以及疾病预后的相关性，探讨其在全身型幼年特发性关节炎（全身型JIA）患者中的功能及预后相关性。
方法：共研究了136例全身型JIA患者，其中包括来自英国儿科风湿病研究小组全国JIA资料库的98例患者以及在意大利帕维亚的圣马泰奥综合医院（IRCCS Policlinico San Matteo）和热那亚的加斯利尼儿童医学研究所（IRCCS G. Gaslini）随访的38例患者。采用SnaPshot ddNTP引物延伸和毛细管电泳对MIF - 173多态性进行基因分型。采用酶联免疫吸附测定法测量MIF水平。仅在随访>5年的意大利患者中评估MIF - 173多态性与预后的相关性，回顾性分析：1）活动性关节炎关节数和活动受限关节数；2）末次就诊时意大利版儿童健康评估问卷（C - HAQ）评分；3）病程中治疗方案相关数据。
结果：携带MIF - 173*C等位基因的全身型JIA患者的MIF血清及滑液水平显著高于GG基因型患者。携带MIF - 173*C等位基因的患者每日糖皮质激素治疗疗程显著长于MIF - 173 GG纯合子患者。此外，携带MIF - 173*C等位基因的患者对关节内注射曲安奈德己酸酯的临床反应持续时间显著较短。在末次就诊时，携带MIF - 173*C等位基因的患者活动性关节炎关节数、C - HAQ评分以及活动受限关节数均显著较高。
结论：我们的研究表明了MIF - 173多态性的功能相关性，并提示MIF - 173*C等位基因是全身型JIA不良预后的一个预测因子。
Objective. To address the functional and prognostic relevance of the -173 single-nucleotide G-to-C polymorphism of the macrophage migration inhibitory factor (MIF) gene in patients with systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) by evaluating its association with serum and synovial fluid levels of MIF, with glucocorticoid requirement, and with the outcome of the disease.Methods. A total of 136 patients with systemic-onset JIA were studied, including 98 patients from the British Paediatric Rheumatology Study Group's National Repository for JIA and 38 patients who were followed up at the IRCCS Policlinico San Matteo (Pavia, Italy) and the IRCCS G. Gaslini (Genoa, Italy). The MIF-173 polymorphism was genotyped using SnaPshot ddNTP primer extension and capillary electrophoresis. MIF levels were measured by enzyme-linked immunosorbent assay. The evaluation of the association of the MIF-173 polymorphism with outcome was performed only in Italian patients who were followed up for >5 years, by analyzing retrospectively 1) the number of joints with active arthritis and the number of joints with limited range of motion; 2) the score, at the last visit, on the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ); and 3) data concerning the treatment regimens during the disease course.Results. Systemic-onset JIA patients carrying a MIF-173*C allele had serum and synovial fluid levels of MIF significantly higher than those in patients with the GG genotype. The duration of glucocorticoid treatment on a daily regimen was significantly longer in patients carrying a MIF-173*C allele than in MIF-173 GG homozygous patients. Moreover, the duration of clinical response. to intraarticular injection of triamcinolone hexacetonide was significantly shorter in patients carrying a MIF-173*C allele. At the last visit, the numbers of joints with active arthritis, the C-HAQ scores, and the numbers of joints with limited range of motion were significantly higher in patients carrying the MIF-173*C allele.Conclusion. Our study shows the functional relevance of the MIF-173 polymorphism and suggests that the MIF-173*C allele is a predictor of poor outcome in systemic-onset JIA.