Sever F, Kobak S, Goksel Ö, Goksel T, Orman M, Berdeli A
a Department of Chest Diseases, Faculty of Medicine , Sifa University , Izmir , Turkey.
b Department of Rheumatology, Faculty of Medicine , Sifa University , Izmir , Turkey.
Scand J Rheumatol. 2016;45(3):215-8. doi: 10.3109/03009742.2015.1092580. Epub 2015 Nov 17.
Sarcoidosis is a chronic granulomatous disease. Pyrin has anti-inflammatory activity in the regulation of inflammasomes and is encoded by the Mediterranean fever (MEFV) gene. MEFV gene mutations trigger the inflammatory cascade and cause familial Mediterranean fever (FMF). A relationship between various rheumatic diseases and MEFV gene mutations has been demonstrated. The aim of this study was to determine the prevalence of the MEFV gene mutation in Turkish patients with sarcoidosis and to detect any possible correlation with disease phenotype.
The study included 78 sarcoidosis patients and 85 healthy subjects matched for age, gender, and ethnicity. MEFV gene mutations were investigated with the FMF strip assay, which is based on reverse hybridization of biotinylated polymerase chain reaction (PCR) products.
Of the 78 patients with sarcoidosis, nine (11.5%) were found to be carriers of MEFV gene mutations. The distribution of these nine mutations were: three (3.8%) V726A, two (2.5%) E148Q, two (2.5%) M680I, one (1.3%) A744S, and one (1.3%) K695R. Carriers of M694V, M694I, R761H, and P369S were not detected in any of the sarcoidosis patients. None of the sarcoidosis patients were found to be compound heterozygous carriers. The prevalence of the MEFV gene mutation carrier detected in the healthy control group was 22.4%. The distribution of the 19 MEFV gene mutations found in the healthy controls was: nine (10.6%) E148Q, two (2.3%) M694V, one (1.2%) M694I, one (1.2%) M680I, two (2.3%) V726A, one (1.2%) A744S, two (2.3%) K695R, and one (1.2%) P369S. When compared with the control group, a lower prevalence of the MEFV gene mutation carrier was found in sarcoidosis patients but this was not statistically significant (p = 0.067). In nine patients found to be MEFV gene mutation carriers, higher serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels and higher numbers patients with arthritis, enthesitis, and ankle arthritis were found (p = 0.01, p = 0.04, p = 0.028, p = 0.05, p = 0.05, respectively).
When we compared Turkish sarcoidosis patients with the healthy control group, we found a lower prevalence of MEFV gene mutations. In sarcoidosis patients, the MEFV gene mutation carrier was found to be related to high acute-phase responses, arthritis, and enthesitis. The existence of MEFV gene mutations may have a preventive role with regard to the development of sarcoidosis. Prospective studies that include larger patient populations are needed.
结节病是一种慢性肉芽肿性疾病。吡啶在炎性小体调节中具有抗炎活性，由地中海热（MEFV）基因编码。MEFV基因突变引发炎症级联反应并导致家族性地中海热（FMF）。已证实多种风湿性疾病与MEFV基因突变之间存在关联。本研究的目的是确定土耳其结节病患者中MEFV基因突变的患病率，并检测其与疾病表型之间的任何可能相关性。
本研究纳入了78例结节病患者和85名年龄、性别及种族相匹配的健康受试者。采用基于生物素化聚合酶链反应（PCR）产物反向杂交的FMF条带分析法对MEFV基因突变进行检测。
在78例结节病患者中，有9例（11.5%）被发现是MEFV基因突变携带者。这9种突变的分布情况为：3例（3.8%）V726A、2例（2.5%）E148Q、2例（2.5%）M680I、1例（1.3%）A744S和1例（1.3%）K695R。在任何结节病患者中均未检测到M694V、M694I、R761H和P369S突变携带者。未发现结节病患者为复合杂合子携带者。在健康对照组中检测到的MEFV基因突变携带者患病率为22.4%。在健康对照组中发现的19种MEFV基因突变的分布情况为：9例（10.6%）E148Q、2例（2.3%）M694V、1例（1.2%）M694I、1例（1.2%）M680I、2例（2.3%）V726A、1例（1.2%）A744S、2例（2.3%）K695R和1例（1.2%）P369S。与对照组相比，结节病患者中MEFV基因突变携带者的患病率较低，但差异无统计学意义（p = 0.067）。在9例被发现为MEFV基因突变携带者的患者中，血清红细胞沉降率（ESR）和C反应蛋白（CRP）水平较高，患关节炎、附着点炎和踝关节关节炎的患者数量较多（分别为p = 0.01、p = 0.04、p = 0.028、p = 0.05、p = 0.05）。
当我们将土耳其结节病患者与健康对照组进行比较时，发现MEFV基因突变的患病率较低。在结节病患者中，MEFV基因突变携带者与高急性期反应、关节炎和附着点炎有关。MEFV基因突变的存在可能对结节病的发生具有预防作用。需要开展纳入更大患者群体的前瞻性研究。
