Radstake Timothy R D J, Sweep Fred C G J, Welsing Paco, Franke Barbara, Vermeulen Sita H H M, Geurts-Moespot Anneke, Calandra Thierry, Donn Rachelle, van Riel Piet L C M
Department of Rheumatology, Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Arthritis Rheum. 2005 Oct;52(10):3020-9. doi: 10.1002/art.21285.
To study whether genetic variants of macrophage migration inhibitory factor (MIF), the MIF -173G>C and CATT(5-8) alleles, are associated with disease severity and levels of circulating MIF in patients with rheumatoid arthritis (RA).
Genotyping was performed in patients with early RA and in healthy controls. Demographic data, disease activity, and outcome measurements were compared between patients with and without the MIF variants. MIF -173G>C and CATT(5-8) polymorphisms were genotyped, and a newly developed enzyme-linked immunosorbent assay for human MIF was used. Allele and genotype distributions of the MIF -173G>C and CATT(5-8) polymorphisms were compared between patients and controls by chi-square test. Multiple regression analysis was performed to assess the independence of the MIF functional genetic variants as risk factors for radiologic joint damage.
Genotyping of the -173G>C and CATT(5-8) polymorphisms of MIF in RA patients and healthy individuals (n = 277 each) revealed similar frequencies of genotypes and haplotypes in both groups. No significant differences in demographic or clinical features were observed between RA patients carrying the MIF -173C allele or the MIF CATT7 allele or both and non-carrier RA patients. Radiologic joint damage was significantly higher in patients carrying risk alleles of the MIF -173G>C or the MIF CATT(5-8) functional variants. No synergistic effects between both genetic variants were observed. Multivariate regression analysis revealed that presence of the MIF -173C/C and MIF CATT(7/7) genotypes and having 1 MIF -173C allele were independent prognostic variables. Carriership of the MIF -173C allele (P = 0.002) or MIF CATT7 allele (P = 0.004) was associated with significantly higher circulating MIF levels compared with those in subjects having none of the risk-conferring alleles, and greater circulating MIF levels correlated with more severe radiologic joint damage (r = 0.64, P = 0.001).
The MIF polymorphisms are not associated with RA susceptibility but are associated with high levels of radiologic joint damage. High circulating MIF levels were shown to correlate strongly with radiologic joint damage, suggesting that MIF expression is genetically determined and can be used as a novel prognostic tool in RA.
研究巨噬细胞移动抑制因子（MIF）的基因变异体，即MIF -173G>C和CATT(5 - 8)等位基因，是否与类风湿关节炎（RA）患者的疾病严重程度及循环中MIF水平相关。
对早期RA患者和健康对照者进行基因分型。比较携带和未携带MIF变异体的患者之间的人口统计学数据、疾病活动度及结局指标。对MIF -173G>C和CATT(5 - 8)多态性进行基因分型，并使用新开发的人MIF酶联免疫吸附测定法。通过卡方检验比较患者和对照者中MIF -173G>C和CATT(5 - 8)多态性的等位基因和基因型分布。进行多元回归分析以评估MIF功能基因变异体作为放射学关节损伤危险因素的独立性。
对RA患者和健康个体（每组n = 277）的MIF的 -173G>C和CATT(5 - 8)多态性进行基因分型，结果显示两组的基因型和单倍型频率相似。携带MIF -173C等位基因或MIF CATT7等位基因或两者的RA患者与未携带者之间在人口统计学或临床特征方面未观察到显著差异。携带MIF -173G>C或MIF CATT(5 - 8)功能变异体风险等位基因的患者放射学关节损伤明显更高。未观察到两种基因变异体之间的协同作用。多变量回归分析显示，MIF -173C/C和MIF CATT(7/7)基因型的存在以及有1个MIF -173C等位基因是独立的预后变量。与没有任何风险等位基因的受试者相比，携带MIF -173C等位基因（P = 0.002）或MIF CATT7等位基因（P = 0.004）与循环MIF水平显著升高相关，且更高的循环MIF水平与更严重的放射学关节损伤相关（r = 0.64，P = 0.001）。
MIF多态性与RA易感性无关，但与高水平的放射学关节损伤相关。高水平的循环MIF与放射学关节损伤密切相关，表明MIF表达由基因决定，可作为RA的一种新的预后工具。
