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Multipl Sklerozisli Hastalarda Serum sFas, sFas Ligand Düzeyleri ile FAS ve FASLG Polimorfizmleri Arasındaki İlişkinin Araştırılması

Year 2020, , 331 - 339, 17.06.2020

Gülay Gülbol Duran İsmet Murat Melek Taşkın Duman Ramazan Güneşaçar

https://doi.org/10.5798/dicletip.755730

Abstract

Amaç: Multiple Sklerozis (MS) otoreaktif T lenfositlerin miyelin antijenlerine karşı gösterdiği reaksiyon sonucu ortaya çıkan otoimmün bir hastalıktır. Fas-FasL yolağı T hücre apoptozisinde önemli bir rol oynamaktadır ve otoimmun hastalıklarda Fas-FasL yolağında defektler olduğu bilinmektedir. Bu çalışmada FAS -670 A/G ve FASLG -844 T/C fonksiyonel gen polimorfizmleri ile serum sFas ve sFasL düzeylerinin MS gelişimine ve hastalığın patogenezine katkısının araştırılması amaçlanmıştır.
Yöntemler: Çalışmaya 108 MS hastası ve kontrol grubu olarak da 98 sağlıklı birey dahil edilmiştir. FAS -670 A/G ve FASLG -844 T/C polimorfizmlerinin belirlenmesi için PCR-RFLP tekniği kullanılmıştır. sFas ve sFasL düzeyleri solid fazlı sandviç ELISA kiti kullanılarak ölçülmüştür.
Bulgular: MS hastalarında FAS -670 AG genotipi frekansı (%55,55) sağlıklı kontrollere (%72,44) göre düşük (p=0.014), GG genotipi frekansı ise hasta grubunda (%19,44) sağlıklı kontrollere (%3,06) göre anlamlı derecede yüksek bulundu (p = 0.0001). Hasta ve kontrol grupları arasında FASLG -844 T/C polimorfizmi açısından anlamlı bir fark bulunamadı (p > 0.05). Serum sFasL düzeyleri MS grubunda, sağlıklı kontrol grubuna göre istatistiksel olarak anlamlı bir şekilde yüksek bulunmakla (p = 0.015) birlikte, sFas düzeyleri gruplar arasında benzer bulundu (p = 0.705). FAS - FASLG polimorfizmleri ile serum sFas - sFasL düzeyleri arasında anlamlı bir ilişki bulunamadı.
Sonuç: Sonuçlarımız FAS -670 AG genotipinin MS riskini azaltarak (RR = 0.475, p = 0.014) koruyucu bir rol oynayabileceğini, GG genotipinin ise MS ile ilişkili güçlü bir risk faktörü (RR = 7.644, p = 0.0001) olabileceğini, serum sFasL düzeylerindeki artışın ise bu faktörün MS patogenezine katkı sunabileceğini gösterebilir.

Keywords

Multiple Sklerozis (MS) Fas Fas Ligand

References

  • 1. Volpe E, Sambucci M, Battistini L, Borsellino G. Fas–Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis. Front Immunol. 2016; 7: 382.
  • 2. Mohammadzadeh A, Pourfathollah AA, Sahraian MA, et al. Evaluation of apoptosis-related genes: Fas (CD94), FasL (CD178) and TRAIL polymorphisms in Iranian multiple sclerosis patients. J Neurol Sci. 2012; 312: 166-9.
  • 3. Xia B, Yu HY, Guo QS, et al. Association of Fas-670 gene polymorphism with inflammatory bowel disease in Chinese patients. World J Gastroenterol. 2005; 11: 415-17.
  • 4. Kim KM, Lee K, Hong YS, Park HY. Fas-mediated apoptosis and expression of related genes in human malignant hematopoietic cells. Exp Mol Med. 2000; 32: 246-54.
  • 5. Kischkel FC, Hellbardt S, Behrmann I, et al. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J. 1995; 14: 5579–88.
  • 6. Gilhar A, Yaniv R, Assy B, et al. Fas pulls the trigger on psoriasis. Am J Pathol. 2006; 168: 170-5.
  • 7. Jalali SA, Shandiz HF, Afshari JT, et al. Status of FAS and FAS Ligand Gene Polymorphisms in Patient with Breast Cancer in Northeastern IRAN. Rep Biochem Mol Biol. 2018; 7: 23-29.
  • 8. Elmore S. Apoptosis: A Review of Programmed Cell Death. Toxicol Pathol. 2007; 35: 495–516.
  • 9. Nagata S, Golstein P. The Fas death factor. Science 1995; 267: 1449-56.
  • 10. Meynier S, Rieux-Laucat F. FAS and RAS related Apoptosis defects: From outoimmunity to leukemia. Immunol Rev, 2019; 287: 50-61
  • 11. Rieux-Laucat F, Magerus-Chatinet A, Neven B. The Autoimmune Lymphoproliferative Syndrome with Defective FAS or FAS-Ligand Functions. J Clin Immunol. 2018; 38: 558-68.
  • 12. Kantarcı OH, Hebrink DD, Achenback SJ, et al. CD95 polymorphisms are associated with susceptibility to MS in women. A population-based study of CD95 and CD95L in MS. J Neuroimmunol. 2004; 146: 162-70.
  • 13. Huang QR, Danis V, Lassere M, Edmonds J, Manolios N. Evaluation of a new Apo-1/Fas promoter polymorphism in rheumatoid arthritis and systemic lupus erythematosus patients. Rheumatology. 1999; 38: 645-51.
  • 14. Fisher GH, Rosenberg FJ, Straus SE, et al. Dominant interfering fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell. 1995; 81: 935-46.
  • 15. Takahashi T, Tanaka M, Inazawa J, et al. Human Fas ligand: gene structure, chromosomal location and species specificity. Int Immunol. 1994; 6: 1567-74.
  • 16. Huang QR, Morris D, Manolios N. Identification and characterization of polymorphisms in the promoter region of the human Apo-1/Fas (CD95) gene. Mol Immunol. 1997; 34: 577-82.
  • 17. Sibley K, Rollinson S, Allan JM, et al. Functional FAS promoter polymorphisms are associated with increased risk of acute myeloid leukemia. Cancer Res. 2003; 63 432: 7-30.
  • 18. Kanemitsu S, Ihara K, Saifddin A, et al. A functional polymorphism in Fas (CD95/APO-1) gene promoter associated with systemic lupus erythematosus. J Rheumatol. 2002; 29: 1183-8.
  • 19. Wu J, Metz C, Xu X, et al. A novel polymorphic CAAT/enhancer-binding protein element in the FasL gene promoter alters Fas ligand expression: a candidate background gene in African American systemic lupus erythematosus patients. J Immunol. 2003; 170: 132-8.
  • 20. van Veen T, Kalkers NF, Crusius JBA, et al. The FAS-670 polymorphism influences susceptibility to multiple sclerosis. J Neuroimmunol. 2002; 128: 95-100.
  • 21. Huang QR, Teutsch SM, Buhler MM et al. Evaluation of the apo-1/Fas promoter mva I polymorphism in multiple sclerosis. Mult Scler. 2000; 6: 14-18.
  • 22. Niino M, Kikuchi S, Fukazawa T, et al. An examination of the Apo-1/Fas promoter Mva I polymorphism in Japanese patients with multiple sclerosis. BMC Neurol. 2002; 2: 8.
  • 23. Mohammadzadeh A, Pourfathollah AA, Sahraian MA, et al. Evaluation of apoptosis-related genes: Fas (CD94), FasL (CD178) and TRAIL polymorphisms in Iranian multiple sclerosis patients. J Neurol Sci. 2012; 312: 166-69.
  • 24. Kaminska J, Koper OM, Piechal K, Kemona H. Multiple sclerosis- etiology and diagnostic potential. Postepy Hig Med Dosw. 2017; 71: 551-63.
  • 25. Sakai T, Inoue A, Koh CS, Osame M. Serum levels of apoptosis-related molecules in patients with multiple sclerosis and human T-lymphotropic virus Type I-associated myelopathy. J Interferon Cytokine Res. 1999; 19: 999-1004.
  • 26. Zipp F, Weller M, Calabresi PA, et al. Increased serum levels of soluble CD95 (APO-1/ Fas) in relapsing-remitting multiple sclerosis. Annals of Neurology. 1998; 43: 116-120.
  • 27. Moreno M, Saenz-Cuesta M, Castillo J, et al. Circulating levels of soluble apoptosis-related molecules in patient with multiple sclerosis. J Neuroimmunol. 2013; 263: 152-4.
  • 28. Ciusani E. Frigerio s, Gelati M, et al. Soluble Fas (Apo-1) levels in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol. 1998; 82: 5-12.

Year 2020, , 331 - 339, 17.06.2020

Gülay Gülbol Duran İsmet Murat Melek Taşkın Duman Ramazan Güneşaçar

https://doi.org/10.5798/dicletip.755730

Abstract

References

  • 1. Volpe E, Sambucci M, Battistini L, Borsellino G. Fas–Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis. Front Immunol. 2016; 7: 382.
  • 2. Mohammadzadeh A, Pourfathollah AA, Sahraian MA, et al. Evaluation of apoptosis-related genes: Fas (CD94), FasL (CD178) and TRAIL polymorphisms in Iranian multiple sclerosis patients. J Neurol Sci. 2012; 312: 166-9.
  • 3. Xia B, Yu HY, Guo QS, et al. Association of Fas-670 gene polymorphism with inflammatory bowel disease in Chinese patients. World J Gastroenterol. 2005; 11: 415-17.
  • 4. Kim KM, Lee K, Hong YS, Park HY. Fas-mediated apoptosis and expression of related genes in human malignant hematopoietic cells. Exp Mol Med. 2000; 32: 246-54.
  • 5. Kischkel FC, Hellbardt S, Behrmann I, et al. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J. 1995; 14: 5579–88.
  • 6. Gilhar A, Yaniv R, Assy B, et al. Fas pulls the trigger on psoriasis. Am J Pathol. 2006; 168: 170-5.
  • 7. Jalali SA, Shandiz HF, Afshari JT, et al. Status of FAS and FAS Ligand Gene Polymorphisms in Patient with Breast Cancer in Northeastern IRAN. Rep Biochem Mol Biol. 2018; 7: 23-29.
  • 8. Elmore S. Apoptosis: A Review of Programmed Cell Death. Toxicol Pathol. 2007; 35: 495–516.
  • 9. Nagata S, Golstein P. The Fas death factor. Science 1995; 267: 1449-56.
  • 10. Meynier S, Rieux-Laucat F. FAS and RAS related Apoptosis defects: From outoimmunity to leukemia. Immunol Rev, 2019; 287: 50-61
  • 11. Rieux-Laucat F, Magerus-Chatinet A, Neven B. The Autoimmune Lymphoproliferative Syndrome with Defective FAS or FAS-Ligand Functions. J Clin Immunol. 2018; 38: 558-68.
  • 12. Kantarcı OH, Hebrink DD, Achenback SJ, et al. CD95 polymorphisms are associated with susceptibility to MS in women. A population-based study of CD95 and CD95L in MS. J Neuroimmunol. 2004; 146: 162-70.
  • 13. Huang QR, Danis V, Lassere M, Edmonds J, Manolios N. Evaluation of a new Apo-1/Fas promoter polymorphism in rheumatoid arthritis and systemic lupus erythematosus patients. Rheumatology. 1999; 38: 645-51.
  • 14. Fisher GH, Rosenberg FJ, Straus SE, et al. Dominant interfering fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell. 1995; 81: 935-46.
  • 15. Takahashi T, Tanaka M, Inazawa J, et al. Human Fas ligand: gene structure, chromosomal location and species specificity. Int Immunol. 1994; 6: 1567-74.
  • 16. Huang QR, Morris D, Manolios N. Identification and characterization of polymorphisms in the promoter region of the human Apo-1/Fas (CD95) gene. Mol Immunol. 1997; 34: 577-82.
  • 17. Sibley K, Rollinson S, Allan JM, et al. Functional FAS promoter polymorphisms are associated with increased risk of acute myeloid leukemia. Cancer Res. 2003; 63 432: 7-30.
  • 18. Kanemitsu S, Ihara K, Saifddin A, et al. A functional polymorphism in Fas (CD95/APO-1) gene promoter associated with systemic lupus erythematosus. J Rheumatol. 2002; 29: 1183-8.
  • 19. Wu J, Metz C, Xu X, et al. A novel polymorphic CAAT/enhancer-binding protein element in the FasL gene promoter alters Fas ligand expression: a candidate background gene in African American systemic lupus erythematosus patients. J Immunol. 2003; 170: 132-8.
  • 20. van Veen T, Kalkers NF, Crusius JBA, et al. The FAS-670 polymorphism influences susceptibility to multiple sclerosis. J Neuroimmunol. 2002; 128: 95-100.
  • 21. Huang QR, Teutsch SM, Buhler MM et al. Evaluation of the apo-1/Fas promoter mva I polymorphism in multiple sclerosis. Mult Scler. 2000; 6: 14-18.
  • 22. Niino M, Kikuchi S, Fukazawa T, et al. An examination of the Apo-1/Fas promoter Mva I polymorphism in Japanese patients with multiple sclerosis. BMC Neurol. 2002; 2: 8.
  • 23. Mohammadzadeh A, Pourfathollah AA, Sahraian MA, et al. Evaluation of apoptosis-related genes: Fas (CD94), FasL (CD178) and TRAIL polymorphisms in Iranian multiple sclerosis patients. J Neurol Sci. 2012; 312: 166-69.
  • 24. Kaminska J, Koper OM, Piechal K, Kemona H. Multiple sclerosis- etiology and diagnostic potential. Postepy Hig Med Dosw. 2017; 71: 551-63.
  • 25. Sakai T, Inoue A, Koh CS, Osame M. Serum levels of apoptosis-related molecules in patients with multiple sclerosis and human T-lymphotropic virus Type I-associated myelopathy. J Interferon Cytokine Res. 1999; 19: 999-1004.
  • 26. Zipp F, Weller M, Calabresi PA, et al. Increased serum levels of soluble CD95 (APO-1/ Fas) in relapsing-remitting multiple sclerosis. Annals of Neurology. 1998; 43: 116-120.
  • 27. Moreno M, Saenz-Cuesta M, Castillo J, et al. Circulating levels of soluble apoptosis-related molecules in patient with multiple sclerosis. J Neuroimmunol. 2013; 263: 152-4.
  • 28. Ciusani E. Frigerio s, Gelati M, et al. Soluble Fas (Apo-1) levels in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol. 1998; 82: 5-12.
There are 28 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Research Article
Authors

Gülay Gülbol Duran This is me

İsmet Murat Melek This is me

Taşkın Duman This is me

Ramazan Güneşaçar This is me

Publication Date June 17, 2020
Submission Date November 5, 2019
Published in Issue Year 2020

Cite

APA Duran, G. G., Melek, İ. M., Duman, T., Güneşaçar, R. (2020). Multipl Sklerozisli Hastalarda Serum sFas, sFas Ligand Düzeyleri ile FAS ve FASLG Polimorfizmleri Arasındaki İlişkinin Araştırılması. Dicle Tıp Dergisi, 47(2), 331-339. https://doi.org/10.5798/dicletip.755730
AMA Duran GG, Melek İM, Duman T, Güneşaçar R. Multipl Sklerozisli Hastalarda Serum sFas, sFas Ligand Düzeyleri ile FAS ve FASLG Polimorfizmleri Arasındaki İlişkinin Araştırılması. diclemedj. June 2020;47(2):331-339. doi:10.5798/dicletip.755730
Chicago Duran, Gülay Gülbol, İsmet Murat Melek, Taşkın Duman, and Ramazan Güneşaçar. “Multipl Sklerozisli Hastalarda Serum SFas, SFas Ligand Düzeyleri Ile FAS Ve FASLG Polimorfizmleri Arasındaki İlişkinin Araştırılması”. Dicle Tıp Dergisi 47, no. 2 (June 2020): 331-39. https://doi.org/10.5798/dicletip.755730.
EndNote Duran GG, Melek İM, Duman T, Güneşaçar R (June 1, 2020) Multipl Sklerozisli Hastalarda Serum sFas, sFas Ligand Düzeyleri ile FAS ve FASLG Polimorfizmleri Arasındaki İlişkinin Araştırılması. Dicle Tıp Dergisi 47 2 331–339.
IEEE G. G. Duran, İ. M. Melek, T. Duman, and R. Güneşaçar, “Multipl Sklerozisli Hastalarda Serum sFas, sFas Ligand Düzeyleri ile FAS ve FASLG Polimorfizmleri Arasındaki İlişkinin Araştırılması”, diclemedj, vol. 47, no. 2, pp. 331–339, 2020, doi: 10.5798/dicletip.755730.
ISNAD Duran, Gülay Gülbol et al. “Multipl Sklerozisli Hastalarda Serum SFas, SFas Ligand Düzeyleri Ile FAS Ve FASLG Polimorfizmleri Arasındaki İlişkinin Araştırılması”. Dicle Tıp Dergisi 47/2 (June 2020), 331-339. https://doi.org/10.5798/dicletip.755730.
JAMA Duran GG, Melek İM, Duman T, Güneşaçar R. Multipl Sklerozisli Hastalarda Serum sFas, sFas Ligand Düzeyleri ile FAS ve FASLG Polimorfizmleri Arasındaki İlişkinin Araştırılması. diclemedj. 2020;47:331–339.
MLA Duran, Gülay Gülbol et al. “Multipl Sklerozisli Hastalarda Serum SFas, SFas Ligand Düzeyleri Ile FAS Ve FASLG Polimorfizmleri Arasındaki İlişkinin Araştırılması”. Dicle Tıp Dergisi, vol. 47, no. 2, 2020, pp. 331-9, doi:10.5798/dicletip.755730.
Vancouver Duran GG, Melek İM, Duman T, Güneşaçar R. Multipl Sklerozisli Hastalarda Serum sFas, sFas Ligand Düzeyleri ile FAS ve FASLG Polimorfizmleri Arasındaki İlişkinin Araştırılması. diclemedj. 2020;47(2):331-9.