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Association of Plasminogen Activator Inhibitor 1 (PAI-1) 4G/5G Polymorphism and Susceptibility to SLE in Egyptian Children and Adolescents: A Multicenter Study
Journal of Inflammation Research ( IF 4.2 ) Pub Date : 2020-12-14 , DOI: 10.2147/jir.s277373
Aly A Yousef 1 , Faisal Y Mohamed 2 , Naglaa F Boraey 3 , Nagwa E Akeel 4 , Attia A Soliman 4 , Nevin M Waked 5 , Mustafa I A Hashem 4 , Hassan Shehata 4 , Dalia S Fahmy 6 , Ali Ismael 7 , Lamya M Ibrahim 8 , Mohamed A M Ibrahim 9 , Hanan F Salem 10 , Sherif M Yousry 11 , Sherif F Osman 12 , Rania A Fouad 13, 14 , Eman T Enan 15, 16 , Mohammed A Attia 17, 18 , Mona R Afify 19 , Nancy M S Zeidan 20 , Mohamed Nashat 21
Affiliation  

Background: 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.
Objective: 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.
Methods: 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.
Results: 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]; P < 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]; P < 0.001, for the 4G/4G genotype and OR: 2.6; [95% CI: 1.85– 3.67]; for the 4G allele; P < 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); P = 0.004.
Conclusion: 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.



中文翻译:

埃及儿童和青少年纤溶酶原激活剂抑制剂 1 (PAI-1) 4G/5G 多态性与 SLE 易感性的关联:一项多中心研究

背景:纤溶酶原激活剂抑制剂-1 (PAI-1) 是连接血栓形成和炎症过程的关键分子。最近,PAI-1 及其基因表达已成为治疗 SLE 等自身免疫性疾病的潜在候选者。
目的:探讨 PAI-1 4G/5G 位点 - 675 的多态性是否可以作为埃及儿童和青少年儿童期发病的 SLE 和狼疮性肾炎易感性的遗传标记。
方法:这项多中心研究纳入了 350 名被诊断患有儿童期 SLE 的患者和 350 名匹配的健康对照者。使用PCR-限制性片段长度多态性(RFLP)对所有受试者进行PAI-1启动子4G/5G多态性在位置-675的基因分型。通过ELISA测量血清PAI-1水平。
结果:与对照组相比,PAI-1 (- 675) 4G/4G 基因型在 c-SLE 患者中更为常见(38% vs 23%;OR =2.7;[95% CI:1.47–2.9];P < 0.001)。携带 PAI-1 4G/4G 基因型或 4G 等位基因的患者更容易患狼疮肾炎(OR:3.38;[95% CI:1.9-5.9];P < 0.001,对于 4G/4G 基因型和 OR:2.6; [95% CI:1.85–3.67];对于 4G 等位基因;P < 0.01)。与 4G/5G 基因型(平均:48.3±16.5 ng/mL)相比,PAI-1 4G/4G 基因型与较高的 PAI-1 血清浓度(平均:86.6±22.7 ng/mL)相关,且 PAI-1 血清浓度最低。对于 5G/5G 基因型(平均值;34.7±11.4 ng/mL);P = 0.004。
结论: PAI-1 4G/5G 多态性可能导致埃及儿童和青少年易患儿童期 SLE 和狼疮性肾炎。此外,PAI-1 4G/4G 基因型和 4G 等位基因与较高的 PAI-1 血清水平和较高的疾病活动评分相关。

更新日期:2020-12-14
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