Çölyak Hastalığı ve Plazminojen Aktivatör İnhibitör-1 Polimorfizminin İlişkisi
Yıl 2022,
Cilt: 32 Sayı: 5, 601 - 604, 29.10.2022
Deniz Ağırbaşlı
,
Minenur Kalyoncu
,
Nur Ramoğlu
,
Zuhal Çalışkan
Öz
Amaç: Çölyak hastalığı (ÇH) otoimmün bir hastalıktır. Çölyak hastalarında tromboza yatkınlık vaka çalışmalarında bildirilmiş olmasına rağmen nedeni henüz bilinmemektedir. Plazminojen aktivatör inhibitörü-1 (PAI-1), fibrinolizi inhibe eder. Bu çalışmada biyopsi ile çölyak tanısı konulmuş kişiler ve sağlıklı kontrollerde çölyak hastalığı ile PAI-1 4G/5G polimorfizmi arasındaki ilişki araştırılmıştır.
Yöntemler: Çalışma için 56 biyopsi ile tanı konulmuş çölyak hastası ve 52 sağlıklı kontrol seçilmiştir. PAI-1 genotiplendirmesi PZR-RFLP metodu ile yapılmış, sonuçlar istatistiksel anlamlılığa göre karşılaştırılmıştır.
Bulgular: Trombotik risk ve enflamasyonla ilişkilendirilen PAI-1 4G aleli vakalarda 5G aleline oranla yüksek bulundu (sırasıyla 0.63 ve 0.36, p=0.054). PAI-1 varyantlarına göre tanı yaşları kıyaslandığında anlamlı bir fark bulunmadı (p=0.3). Genotip olarak 4G/4G hastalar ve kontrollerde benzer olsa da koruyucu genotip olarak bilinen 5G/5G genotipi kontrollerde hastalara kıyasla yüksek bulunmuştur (35% ve 18%).
Sonuç: Çalışmamızda çölyak hastalarında kontrol guruba göre PAI-1’in tromboza yatkınlıkta rol oynayan 4G aleli daha sık gözlenmiştir. Çölyak hastalarında tromboz genetik belirteçlerinin çalışılması bireysel proflaksi açısından önem taşımaktadır.
Destekleyen Kurum
Acıbadem Mehmet Ali Aydınlar University
Proje Numarası
ABAPKO Decision Number :2017/01/06.
Kaynakça
- Referans1 Farrell RJ, Kelly CP. Celiac sprue. N Engl J Med 2002;346(03):180–88.
- Referans2 Gujral N, Freeman HJ, Thomson ABR. Celiac disease: Prevalence, diagnosis, pathogenesis and treatment World J Gastroenterol. 2012;18(42):6036–59.
- Referans3 ESPGN Group: Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child 1990;65:909-11
- Referans4 Ghannouchi Jaafoura N, Atig A, Bouker A, Alaoua O, Ben Jazia E, Khalifa M, Bahri F. Intracardiac thrombosis during celiac disease. J Mal Vasc. 2014;39(3):203-6.
- Referans5 Lerner A, Blank M. Hypercoagulability in celiac disease--an update. Autoimmun Rev. 2014;13(11):1138-41.
- Referans6 Agirbasli M. Pivotal role of plasminogen-activator inhibitor 1 in vascular disease. Int J Clin Pract 2005;59(1):102-6.
- Referans7 Flevaris P, Vaughan D.The Role of Plasminogen Activator Inhibitor Type-1 in Fibrosis. Semin Thromb Hemost. 2017;43(2):169-77.
- Referans8 Wang ZH, Ren WY, Zhu L, Hu LJ. Plasminogen activator inhibitor-1 regulates LPS induced inflammation in rat macrophages through autophagy activation. Sci World J. 2014;2014:189168.
- Referans9 Pham BT, van Haaften WT, Oosterhuis D, Nieken J, de Graaf IA, Olinga P. Precision-cut rat, mouse, and human intestinal slices as novel models for the early-onset of intestinal fibrosis. Physiol Rep. 2015;3(4). pii: e12323
- Referans10 Eriksson P, Kallin B, van 't Hooft F M, Båvenholm P, and Hamsten A. Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci U S A. 1995;92(6):1851–55.
- Referans11 Rossaak JI, Van Rij AM, Jones GT, Harris EL. Association of the 4G/5G polymorphism in the promoter region of the plasminogen activator inhibitor-1 with abdominal aortic aneurysms. J Vasc Surg 2000;31:1026–32.
- Referans12 Ludvigsson JF, Welander A, Lassila R, Ekbom A, Montgomery SM. Risk of thromboembolism in 14,000 individuals with coeliac disease. Br J Haematol 2007;139(01):121–7.
- Referans13 Ciacci C, Tortora R, Scudiero O, Di Fiore R, Salvatore F, Castaldo G. Early pregnancy loss in celiac women: The role of genetic markers of thrombophilia. Dig Liver Dis. 2009;41(10):717-20.
- Referans14 Picchi A1, Pasqualini P, D'Aiello I, Cortese B, Micheli A, Limbruno U. Acute ST-elevation myocardial infarction in a 15-year-old boy with celiac disease and multifactorial thrombotic risk. Thromb Haemost. 2008 Jun;99(6):1116-8.
- Referans15 Zimmerman M, Rolandsson E, Skärstrand H, Pourhamidi K, Gottsäter A, Wollmer P, Rolandsson O, Westergren-Thorsson G, Dahlin LB. Temporal trend of autonomic nerve function and HSP27, MIF and PAI-1 in type 1 diabetes. J Clin Transl Endocrinol. 2017;8:15-21.
- Referans16 Grabarczyk E1, Szaflarska-Popławska A, Góralczyk K, Rość D. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in children with ulcerative colitis. Pol Merkur Lekarski. 2006;20(117):326-8.
- Referans17 Berthoux E, Fabien N, Chayvialle JA, Ninet J, Durieu I. Adult celiac disease with thrombosis: a case series of seven patients. Role of thrombophilic factors. Rev Med Interne 2011;32(10):600–604.
Association of Celiac Disease and Plasminogen Activator Inhibitor-1 Polymorphism
Yıl 2022,
Cilt: 32 Sayı: 5, 601 - 604, 29.10.2022
Deniz Ağırbaşlı
,
Minenur Kalyoncu
,
Nur Ramoğlu
,
Zuhal Çalışkan
Öz
Objective: Celiac disease (CD) is an autoimmune disease. Although susceptibility to thrombosis in celiac patients has been reported in case studies, the cause is not yet known. PAI-1 inhibits fibrinolysis. In this study, the association between celiac disease and PAI-1 4G/5G polymorphism was investigated among celiac patients whose disease were confirmed by intestinal biopsy and healthy controls.
Methods: Biopsy-diagnosed celiac patients (n=56) and healthy controls (n=52) were included in the study. PCR-RFLP method was used for PAI-1 genotyping and the results were compared according to statistical significance.
Results: The PAI-1 4G allele associated with thrombotic risk and inflammation was found to be higher than the 5G allele in cases (0.63 and 0.36, respectively, p=0.054). When the age at diagnosis was compared according to the PAI-1 variants, no significant difference was found (p=0.3). Although the genotype frequencies were similar in 4G/4G patients and controls, the 5G/5G genotype, known as the protective genotype, was found to be higher in controls (35% and 18%).
Conclusion: In our study, the 4G allele of PAI-1, which plays a role in the susceptibility to thrombosis, was observed more frequently in celiac patients compared to the control group. Studying genetic markers of thrombosis in celiac patients is important for individual prophylaxis.
Proje Numarası
ABAPKO Decision Number :2017/01/06.
Kaynakça
- Referans1 Farrell RJ, Kelly CP. Celiac sprue. N Engl J Med 2002;346(03):180–88.
- Referans2 Gujral N, Freeman HJ, Thomson ABR. Celiac disease: Prevalence, diagnosis, pathogenesis and treatment World J Gastroenterol. 2012;18(42):6036–59.
- Referans3 ESPGN Group: Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child 1990;65:909-11
- Referans4 Ghannouchi Jaafoura N, Atig A, Bouker A, Alaoua O, Ben Jazia E, Khalifa M, Bahri F. Intracardiac thrombosis during celiac disease. J Mal Vasc. 2014;39(3):203-6.
- Referans5 Lerner A, Blank M. Hypercoagulability in celiac disease--an update. Autoimmun Rev. 2014;13(11):1138-41.
- Referans6 Agirbasli M. Pivotal role of plasminogen-activator inhibitor 1 in vascular disease. Int J Clin Pract 2005;59(1):102-6.
- Referans7 Flevaris P, Vaughan D.The Role of Plasminogen Activator Inhibitor Type-1 in Fibrosis. Semin Thromb Hemost. 2017;43(2):169-77.
- Referans8 Wang ZH, Ren WY, Zhu L, Hu LJ. Plasminogen activator inhibitor-1 regulates LPS induced inflammation in rat macrophages through autophagy activation. Sci World J. 2014;2014:189168.
- Referans9 Pham BT, van Haaften WT, Oosterhuis D, Nieken J, de Graaf IA, Olinga P. Precision-cut rat, mouse, and human intestinal slices as novel models for the early-onset of intestinal fibrosis. Physiol Rep. 2015;3(4). pii: e12323
- Referans10 Eriksson P, Kallin B, van 't Hooft F M, Båvenholm P, and Hamsten A. Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci U S A. 1995;92(6):1851–55.
- Referans11 Rossaak JI, Van Rij AM, Jones GT, Harris EL. Association of the 4G/5G polymorphism in the promoter region of the plasminogen activator inhibitor-1 with abdominal aortic aneurysms. J Vasc Surg 2000;31:1026–32.
- Referans12 Ludvigsson JF, Welander A, Lassila R, Ekbom A, Montgomery SM. Risk of thromboembolism in 14,000 individuals with coeliac disease. Br J Haematol 2007;139(01):121–7.
- Referans13 Ciacci C, Tortora R, Scudiero O, Di Fiore R, Salvatore F, Castaldo G. Early pregnancy loss in celiac women: The role of genetic markers of thrombophilia. Dig Liver Dis. 2009;41(10):717-20.
- Referans14 Picchi A1, Pasqualini P, D'Aiello I, Cortese B, Micheli A, Limbruno U. Acute ST-elevation myocardial infarction in a 15-year-old boy with celiac disease and multifactorial thrombotic risk. Thromb Haemost. 2008 Jun;99(6):1116-8.
- Referans15 Zimmerman M, Rolandsson E, Skärstrand H, Pourhamidi K, Gottsäter A, Wollmer P, Rolandsson O, Westergren-Thorsson G, Dahlin LB. Temporal trend of autonomic nerve function and HSP27, MIF and PAI-1 in type 1 diabetes. J Clin Transl Endocrinol. 2017;8:15-21.
- Referans16 Grabarczyk E1, Szaflarska-Popławska A, Góralczyk K, Rość D. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in children with ulcerative colitis. Pol Merkur Lekarski. 2006;20(117):326-8.
- Referans17 Berthoux E, Fabien N, Chayvialle JA, Ninet J, Durieu I. Adult celiac disease with thrombosis: a case series of seven patients. Role of thrombophilic factors. Rev Med Interne 2011;32(10):600–604.