Marinko Artuković, Clinical Hospital Sveti Duh, Ul. Sveti Duh 64, 10000 Zagreb, Croatia,
Croat Med J. 2020 Dec 31;61(6):547-555. doi: 10.3325/cmj.2020.61.547.
To investigate the association of FasL gene polymorphism (rs763110) with rheumatoid arthritis occurrence, disease activity, and tumor necrosis factor-α (TNF-α) plasma concentration in Croatian patients, and to conduct an updated meta-analysis.
This cross-sectional study enrolled 81 patients with rheumatoid arthritis and 94 control patients. After the assessment of the Disease Activity Score (DAS)-28, blood was taken for analysis. DNA was isolated from the whole blood to determine FasL polymorphism (rs763110) by polymerase chain reaction. Protein levels of TNF-α were determined with ELISA. After a detailed literature search, we conducted an updated meta-analysis using the Review Manager 5 software.
Rheumatoid arthritis patients had significantly higher TNF-α concentration in plasma (1.65 [1.2-2.42] pg/mL) than controls (0.99 [0.77-1.35] pg/mL, P<0.001). The FasL rs763110 polymorphism was not associated with rheumatoid arthritis occurrence in either codominant, dominant, recessive, overdominant, or log additive model. Furthermore, the rs763110 genotype was not associated with DAS 28 score or TNF-α concentration. After we added our results to an updated meta-analysis, the significant association previously reported for Western Eurasians was abolished.
Our data suggest that the association between FasL rs763110 polymorphism and RA susceptibility in Western Eurasians observed in previous studies might be overestimated and should be limited to the population of Southwestern Asia until further investigations are performed.
探讨 FasL 基因多态性(rs763110)与克罗地亚类风湿关节炎患者发病、疾病活动度和肿瘤坏死因子-α(TNF-α)血浆浓度的关系,并进行更新的荟萃分析。
本横断面研究纳入了 81 例类风湿关节炎患者和 94 例对照患者。在评估疾病活动评分(DAS)-28 后,采集血液进行分析。从全血中提取 DNA,通过聚合酶链反应确定 FasL 多态性(rs763110)。采用酶联免疫吸附试验测定 TNF-α的蛋白水平。经过详细的文献检索,我们使用 Review Manager 5 软件进行了更新的荟萃分析。
与对照组(0.99 [0.77-1.35] pg/mL,P<0.001)相比,类风湿关节炎患者血浆中 TNF-α浓度显著升高(1.65 [1.2-2.42] pg/mL)。在共显性、显性、隐性、超显性或对数相加模型中,FasL rs763110 多态性与类风湿关节炎的发生均无相关性。此外,rs763110 基因型与 DAS 28 评分或 TNF-α浓度无关。当我们将结果加入更新的荟萃分析中时,先前报道的与西方欧亚人有关的 FasL rs763110 多态性与 RA 易感性的显著相关性被消除。
我们的数据表明,先前研究中观察到的 FasL rs763110 多态性与西方欧亚人 RA 易感性之间的关联可能被高估,并且应该仅限于西南亚人群,直到进一步研究为止。