Association of Plasminogen Activator Inhibitor 1 (PAI-1) 4G/5G Polymorphism and Susceptibility to SLE in Egyptian Children and Adolescents: A Multicenter Study

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 IA Hashem,4 Hassan Shehata,4 Dalia S Fahmy,6 Ali Ismael,7 Lamya M Ibrahim,8 Mohamed AM Ibrahim,9 Hanan F Salem,10 Sherif M Yousry,11 Sherif F Osman,12 Rania A Fouad,13,14 Eman T Enan,15,16 M...

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Autores principales: Yousef AA, Mohamed FY, Boraey NF, Akeel NE, Soliman AA, Waked NM, Hashem MIA, Shehata H, Fahmy DS, Ismael A, Ibrahim LM, Ibrahim MAM, Salem HF, Yousry SM, Osman SF, Fouad RA, Enan ET, Attia MA, Afify MR, Zeidan NMS, Nashat M
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2020
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sle
Acceso en línea:https://doaj.org/article/1abd069844a54c6894f02e1129a8c57d
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Sumario: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 IA Hashem,4 Hassan Shehata,4 Dalia S Fahmy,6 Ali Ismael,7 Lamya M Ibrahim,8 Mohamed AM 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 MS Zeidan,20 Mohamed Nashat21 1Department of Pediatrics, Faculty of Medicine, Helwan University, Helwan, Egypt; 2Department of Pediatrics, Faculty of Medicine, Ain-Shams University, Cairo, Egypt; 3Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, Egypt; 4Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 5Department of Pediatrics, Faculty of Medicine, October 6 University, October 6, Egypt; 6Department of Rheumatology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 7Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 8Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 9Department of Clinical Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt; 10Department of Anesthesia, Faculty of Medicine, Banha University, Banha, Egypt; 11Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt; 12Department of Radiology, Texas Tech University Health Sciences Center, El Paso, TX, USA; 13Department of Medical Biochemistry, College of Medicine, El-Mareefa University, Riyadh, Kingdom of Saudi Arabia; 14Department of Medical Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 15Department of Pathology, College of Medicine, El-Mareefa University, Riyadh, Kingdom of Saudi Arabia; 16Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt; 17Department of Clinical Pharmacology, College of Medicine, El-Mareefa University, Riyadh, Kingdom of Saudi Arabia; 18Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt; 19Department of Medical microbiology and Parasitology, Faculty of Medicine, University of Jeddah, Jeddah, 21589, Saudia Arabia; 20Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt; 21Department of Pediatrics, Faculty of Medicine, Aswan University, Aswan, EgyptCorrespondence: Faisal Y MohamedFaculty of Medicine, Ain-Shams University, Cairo, EgyptTel +201113363638Email Faisalyousef69@gmail.comBackground: 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.Keywords: plasminogen activator inhibitor-1, PAI-1, gene polymorphism, SLE, children, adolescents