Yousef Aly A, Mohamed Faisal Y, Boraey Naglaa F, Akeel Nagwa E, Soliman Attia A, Waked Nevin M, Hashem Mustafa I A, Shehata Hassan, Fahmy Dalia S, Ismael Ali, Ibrahim Lamya M, Ibrahim Mohamed A M, Salem Hanan F, Yousry Sherif M, Osman Sherif F, Fouad Rania A, Enan Eman T, Attia Mohammed A, Afify Mona R, Zeidan Nancy M S, Nashat Mohamed
Department of Pediatrics, Faculty of Medicine, Helwan University, Helwan, Egypt.
Department of Pediatrics, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
J Inflamm Res. 2020 Dec 14;13:1103-1111. doi: 10.2147/JIR.S277373. eCollection 2020.
Plasminogen activator inhibitor-1 (PAI-1) is a key molecule residing at the nexus between thrombosis and inflammatory processes. Recently, PAI-1 and its gene expression have emerged as a potential candidate for autoimmune disorders such as SLE.
To investigate whether the PAI-1 4G/5G polymorphism at position -675 could be a genetic marker for susceptibility to childhood-onset SLE and development of lupus nephritis among Egyptian children and adolescents.
Three hundred fifty patients diagnosed with childhood-onset SLE and 350 well-matched healthy controls were included in this multi-center study. All subjects were genotyped for the PAI-1 promoter 4G/5G polymorphism at position -675 using PCR- restriction fragment length polymorphism (RFLP). Serum PAI-1 levels were measured by ELISA.
The PAI-1 (- 675) 4G/4G genotype was more represented in c-SLE patients, as compared to the control group (38% vs 23%; OR =2.7; [95% CI: 1.47-2.9]; < 0.001). Patients carrying the PAI-1 4G/4G genotype or 4G allele were more likely to develop lupus nephritis (OR: 3.38; [95% CI: 1.9-5.9]; <0.001, for the 4G/4G genotype and OR: 2.6; [95% CI: 1.85-3.67]; for the 4G allele; < 0.01). The PAI-1 4G/4G genotype was associated with higher PAI-1 serum concentrations (mean; 86.6±22.7 ng/mL) as compared to those with a 4G/5G genotype (mean; 48.3±16.5 ng/mL) and the lowest for the 5G/5G genotype (mean; 34.7±11.4 ng/mL); = 0.004.
The PAI-1 4G/5G polymorphism may confer susceptibility to childhood-onset SLE and development of lupus nephritis among Egyptian children and adolescents. Moreover, the PAI-1 4G/4G genotype and 4G allele were associated with higher PAI-1 serum levels and higher disease activity scores.
纤溶酶原激活物抑制剂-1（PAI-1）是血栓形成和炎症过程之间联系的关键分子。最近，PAI-1及其基因表达已成为自身免疫性疾病（如系统性红斑狼疮）的潜在候选因素。
研究-675位的PAI-1 4G/5G多态性是否可能是埃及儿童和青少年儿童期起病系统性红斑狼疮易感性及狼疮性肾炎发生的遗传标志物。
本多中心研究纳入350例诊断为儿童期起病系统性红斑狼疮的患者和350例匹配良好的健康对照。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对所有受试者进行-675位PAI-1启动子4G/5G多态性基因分型。通过酶联免疫吸附测定法（ELISA）测量血清PAI-1水平。
与对照组相比，c-SLE患者中PAI-1（-675）4G/4G基因型的比例更高（38%对23%；比值比=2.7；[95%置信区间：1.47-2.9]；P<0.001）。携带PAI-1 4G/4G基因型或4G等位基因的患者更易发生狼疮性肾炎（对于4G/4G基因型，比值比：3.38；[95%置信区间：1.9-5.9]；P<0.001；对于4G等位基因，比值比：=2.6；[95%置信区间：1.85-3.67]；P<0.01）。与4G/5G基因型（平均值：48.3±16.5 ng/mL）和5G/5G基因型（最低，平均值：34.7±11.4 ng/mL）相比，PAI-1 4G/4G基因型与更高的PAI-1血清浓度相关（平均值：86.6±22.7 ng/mL）；P=0.004。
PAI-1 4G/5G多态性可能使埃及儿童和青少年易患儿童期起病的系统性红斑狼疮及狼疮性肾炎。此外,PAI-4G/4G基因型和4G等位基因与更高的PAI-1血清水平和更高的疾病活动评分相关。
