An unexpectedly high frequency of MEFV mutations in patients with anti-citrullinated protein antibody-negative palindromic rheumatism
An unexpectedly high frequency of MEFV mutations in patients with anti-citrullinated protein antibody-negative palindromic rheumatism
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DOI：
10.1002/art.22755
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发表时间：
2007-08-01
影响因子：
--
通讯作者：
Yague, Jordi
中科院分区：
文献类型：
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作者：
Canete, Juan D.;Arostegui, Juan I.;Yague, Jordi
目标。MEFV基因参与炎症反应的调节，并与家族性地中海热（FMF）和间歇性关节水肿有关，目的是研究MEFV基因是否与复发性风湿病（PR）的发病机制有关，并在西班牙一组PR患者中研究其临床表现及其演变。从病历和个人访谈中收集了75例诊断为PR的患者的家族史、人口统计学临床资料和实验室特征。健康对照组包括325名血库献血者。FMF对照组由84名西班牙FMF患者组成。分离基因组DNA，采用聚合酶链反应扩增和序列分析进行MEFV基因突变分析。65名不相关的PR患者最终被纳入研究。MEFV基因突变分析发现，65例患者中有8例（12.3%）携带至少1个MEFV等位基因突变。MEFV突变患者的平均年龄和发病年龄较高，但抗瓜氨酸蛋白抗体（ACPAs）的平均血清水平较低。在有突变的患者和没有突变的患者之间没有观察到其他显著差异。acpa阴性PR患者MEFV突变频率为22.2%，而acpa阳性PR患者为5.3% （P = 0.058）。该研究显示，在acpa阴性PR患者中，MEFV基因突变的发生率较高，这支持了它可能是一种易感基因的假设。我们的研究结果也支持了MEFV基因可能参与其他未分化复发性炎性风湿病发病机制的假设。
Objective. To investigate whether the MEFV gene, which is involved in the regulation of the inflammatory response and has been associated with familial Mediterranean fever (FMF) and intermittent hydrarthrosis, is implicated in the pathogenesis of palindromic rheumatism (PR) and to examine its clinical presentation and its evolution in a Spanish cohort of PR patients.Methods. Family histories, demographic clinical data, and laboratory characteristics of 75 patients diagnosed as having PR were collected from medical records and personal interviews. The healthy control group included 325 blood bank donors. The FMF control group was made up of 84 Spanish FMF patients. Genomic DNA was isolated, and MEFV gene mutation analysis was performed by polymerase chain reaction amplification and sequence analysis.Results. Sixty-five unrelated PR patients were finally included in the study. MEFV gene mutation analysis identified 8 of these 65 patients (12.3%) as carriers of at least I mutated MEFV allele. Patients with MEFV mutations had higher mean age and age at disease onset, but lower mean serum levels of anti-citrullinated protein antibodies (ACPAs). No other significant differences were observed between patients with and those without mutations. The frequency of MEFV mutations in ACPA-negative PR patients was 22.2%, compared with 5.3% in ACPA-positive PR patients (P = 0.058).Conclusion. This study shows a previously unreported high prevalence of mutations of the MEFV gene in patients with ACPA-negative PR. This supports the hypothesis that it might be a susceptibility gene. Our findings also support the hypothesis that the MEFV gene might participate in the pathogenesis of other undifferentiated relapsing inflammatory rheumatic disorders.