Department of Rheumatology, Faculty of Medicine, Firat University, 23119 Elazig, Turkey.
Joint Bone Spine. 2010 Jan;77(1):32-5. doi: 10.1016/j.jbspin.2009.08.006. Epub 2009 Dec 23.
Pyrin/marenostrin, an inhibitory regulator of inflammation, is encoded by MEditerranean FeVer (MEFV) gene. Mutations of this gene are the cause of familial Mediterranean fever (FMF). A connection between MEFV gene mutations and rheumatic diseases has been suggested. The aim of this study was to explore the frequency and clinical significance of MEFV gene mutations in a cohort of Turkish patients with rheumatoid arthritis (RA).
The study included 103 patients with RA and 103 age-, sex- and origin-matched healthy controls (HC). In all participants, genomic DNA was isolated and genotyped using amplification refractory mutation system or restriction fragment length polymorphism for the eight MEFV gene mutations (E148Q, M694V, M694I, M680I, V726A, A744S, R761H, and P369S). In the RA group, disease activity was determined using the disease activity score-28 (DAS-28), and radiological damage was evaluated by the modified Larsen scoring method.
Carrier rates of MEFV gene mutations were 26/103 (25.2%) and 24/103 (23.3%) in the RA and HC groups, respectively (p>0.05, OR: 0.9, 95% CI: 0.48-1.71). In the RA group, while deformed joint count was significantly higher in the mutation carrier group than those of the non-carrier group (p<0.05), the level of C-reactive protein, DAS-28 and modified-Larsen scores were slightly but not significantly higher in the carrier group.
The results of this study suggest that MEFV gene mutations appear to be an aggravating factor for the severity of RA, and consequently, patients with RA might be screened for MEFV gene mutations in countries where FMF is frequent. Whether the searching of MEFV gene mutations in RA patients is cost-effective deserves further investigations.
吡嗪/马伦斯特林是一种炎症抑制调节因子，由 Mediterranean Fever（MEFV）基因编码。该基因的突变是家族性地中海热（FMF）的病因。已经有人提出 MEFV 基因突变与风湿性疾病之间存在关联。本研究的目的是在土耳其类风湿关节炎（RA）患者队列中探讨 MEFV 基因突变的频率及其临床意义。
该研究纳入了 103 例 RA 患者和 103 名年龄、性别和来源匹配的健康对照者（HC）。在所有参与者中，使用扩增受阻突变系统或限制性片段长度多态性方法对 8 种 MEFV 基因突变（E148Q、M694V、M694I、M680I、V726A、A744S、R761H 和 P369S）进行基因分型。在 RA 组中，采用疾病活动评分 28（DAS-28）评估疾病活动度，并采用改良 Larsen 评分法评估放射学损害。
RA 组和 HC 组的 MEFV 基因突变携带者率分别为 26/103（25.2%）和 24/103（23.3%）（p>0.05，OR：0.9，95%CI：0.48-1.71）。在 RA 组中，突变携带者组的畸形关节计数明显高于非携带者组（p<0.05），而携带者组的 C 反应蛋白、DAS-28 和改良 Larsen 评分仅略高，但无统计学意义。
本研究结果表明，MEFV 基因突变似乎是 RA 严重程度的加重因素，因此在 FMF 高发国家，RA 患者可能需要进行 MEFV 基因突变筛查。在 RA 患者中筛查 MEFV 基因突变是否具有成本效益值得进一步研究。
