Investigation of the Relation Between FAS, FASLG Polymorphisms and Serum Fas, FasL Levels in Patients with Psoriasis

Duran, Gülay Gülbol; Kasap, Mulkiye; Gunesacar, Ramazan; Dogramacı, Asena Cigdem; Denli, Yasar Gul

doi:10.2478/rrlm-2018-0024

Abstract

Background: Psoriasis is a multifactorial and inflammatory chronic skin disease indicated with T-cell-mediated keratinocyte hyper-proliferation. Demographic, epidemiological (family, twin), serological, and genetic studies have clearly demonstrated that psoriasis is a polygenic and multifactorial disease.

Aim: The objectives of the study are; to determine the prevalence of the polymorphisms of FAS (Fas cell surface receptor gene) -671 A>G (rs:1800682) and FASLG (Fas ligand gene) -844 T>C (rs:763110), to investigate the serum levels of sFas and sFasL, and also to discover any relationship between gene polymorphisms and serum levels in psoriatic patients.

Material and Methods: 50 treated and 69 untreated patients, and 140 healthy controls were included in the study. Polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The serum levels were measured in randomly selected treated (39) and untreated (40) patients, also in 84 healthy controls using micro-ELISA technique.

Results: There was no statistical difference between polymorphisms in the patient and control groups. However, sFas and sFasL levels in both treated and untreated patients were higher than that of the controls.

Conclusion: The investigated FAS and FASLG polymorphisms were not found to be directly associated with the psoriasis. Elevated sFas and sFasL levels in psoriatic patients showed that these factors may possess a significant role in the pathogenesis of psoriasis.

References

1. Langley RG, Krueger GG, Griffiths CE. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis. 2005;64 Suppl 2: ii18-ii23. DOI: 10.1136/ard.2004.03321710.1136/ard.2004.033217
Open DOI Search in Google Scholar Back to article
2. Erkek E. Psoriazis Etyopatogenezi. Turkiye Klinikleri J Dermatol-Special Topics. 2008;1(3):1-14.
Search in Google Scholar Back to article
3. Roman II, Orasan MS, Coneac A, Marina EM, Pop AD, Orasan RI. Genetic and Hormonal Determinations in a Pair of Identical Twins with Early Onset Psoriasis Vulgaris: Case Report and a Brief Review of the Literature. Rev Romana Med Lab. 2017; 25(3):287-94 DOI: 10.1515/rrlm-2017-002110.1515/rrlm-2017-0021
Open DOI Search in Google Scholar Back to article
4. Oskay T, Erdem C. Apopitoz ve Dermatolojideki Önemi. Turkiye Klinikleri J Dermatol. 2000;10(3):213-21.
Search in Google Scholar Back to article
5. Ada S. Psoriazis Sistemik Bir Hastalık mıdır? Turkiye Klinikleri J Dermatol-Special Topics. 2008;1(3):45-8.
Search in Google Scholar Back to article
6. Oskay T, KundakçI N. Psoriasisde genetik bulgular. Turkiye Klinikleri J Dermatol. 2000;10(2):139-45.
Search in Google Scholar Back to article
7. Asgari R, Yari K, Mansouri K, Bakhtiari M. Association analysis of FAS -670 A/G and FASL -844 C/T polymorphisms with risk of generalized agressive periodontitis disease. Biomed Rep. 2018;8 (4): 391-395.10.3892/br.2018.1060
Search in Google Scholar Back to article
8. Ozdemirkiran FG, Nalbantoglu S, Gokgoz Z, Payzin BK, Vural F, Cagiran S, Berdeli A. FAS/FASL gene polymorphisms in Turkish patients with chronic myeloproliferative disorders. Arch Med Sci. 2017;13(2): 426-432. DOI: 10.5114/aoms.2015.5396310.5114/aoms.2015.53963
Search in Google Scholar Back to article
9. Gilhar A, Yaniv R, Assy B, Serafimovich S, Ull-mann Y, Kalish RS. Fas pulls the trigger on psoriasis. Am J Pathol. 2006;168(1):170-5. DOI: 10.2353/aj-path.2006.04135410.2353/aj-path.2006.041354
Open DOI Search in Google Scholar Back to article
10. Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science. 1998;281(5381):1305-8. DOI: 10.1126/science.281.5381.130510.1126/science.281.5381.1305
Search in Google Scholar Back to article
11. Fisher GH, Rosenberg FJ, Straus SE, Dale JK, Middleton LA, Lin AY, et al. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell. 1995;81(6):935-46. DOI: 10.1016/0092-8674(95)90013-610.1016/0092-8674(95)90013-6
Open DOI Search in Google Scholar Back to article
12. 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(8-9):577-82. DOI: 10.1016/S0161-5890(97)00081-310.1016/S0161-5890(97)00081-3
Open DOI Search in Google Scholar Back to article
13. Kanemitsu S, Ihara K, Saifddin A, Otsuka T, Takeuchi T, Nagayama J, et al. A functional polymorphism in fas (CD95/APO-1) gene promoter associated with systemic lupus erythematosus. J Rheumatol. 2002;29(6):1183-8.
Search in Google Scholar Back to article
14. Wu J, Metz C, Xu X, Abe R, Gibson AW, Edberg JC, et al. A novel polymorphic CAAT/enhancer-binding protein beta 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(1):132-8. DOI: 10.4049/jimmunol.170.1.13210.4049/jimmunol.170.1.13212496392
Search in Google Scholar Back to article
15. Seishima M, Seishima M, Takemura M, Saito K, Kitajima Y. Increased serum soluble Fas, tumor necrosis factor alpha and interleukin 6 concentrations in generalized pustular psoriasis. Dermatology. 1998;196(3):371-2.
Search in Google Scholar Back to article
16. Mysliwiec H, Baran A, Mysliwiec P, Gorska M, Flisiak I. Upregulation of the sFas/sFasL system in psoriatic patients. Add Med Sci. 2015;60(1):64-8. DOI: 10.1016/j.advms.2014.10.00510.1016/j.advms.2014.10.00525437350
Search in Google Scholar Back to article
17. Sibley K, Rollinson S, Allan JM, Smith AG, Law GR, Roddam PL, et al. Functional FAS promoter polymorphisms are associated with increased risk of acute myeloid leukemia. Cancer Res. 2003;63(15):4327-30.
Search in Google Scholar Back to article
18. Xia B, Yu YH, Guo QS, Li XY, Jiang L, Li J. Association of Fas-670 gene polymorphism with inflammatory bowel disease in Chinese patients. World J Gastroenterol. 2005;11(3):415-7. DOI: 10.3748/wjg.v11.i3.41510.3748/wjg.v11.i3.415420535115637757
Open DOI Search in Google Scholar Back to article
19. Sun T, Zhou Y, Li H, Han X, Shi Y, Wang L, et al. FASL–844C polymorphism is associated with increased activation-induced T cell death and risk of cervical cancer. J Exp Med. 2005;202(7):967-74. DOI: 10.1084/jem.2005070710.1084/jem.20050707
Open DOI Search in Google Scholar Back to article
20. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215. DOI: 10.1093/nar/16.3.121510.1093/nar/16.3.1215
Open DOI Search in Google Scholar Back to article
21. Ozel EG, Duran GG, Celik MM, Duran N, Gunesacar R. Fas and Fas ligand gene polymophisims in Turkish patient with Familial Mediterranean Fever. Gene. 2017; 623:29-32. DOI: 10.1016/j.gene.2017.04.03710.1016/j.gene.2017.04.037
Open DOI Search in Google Scholar Back to article
22. Ghoreschi K, Mrowietz U, Röcken M. A molecule solves psoriasis? Systemic therapies for psoriasis inducing interleukin 4 and Th2 responses. J Mol Med. 2003;81(8):471-80. DOI: 10.1007/s00109-003-0460-910.1007/s00109-003-0460-9
Open DOI Search in Google Scholar Back to article
23. Allombert-Blaise C, Tamiji S, Mortier L, Fauvel H, Tual M, Delaporte E, et al. Terminal differentiation of human epidermal keratinocytes involves mitochondria- and caspase-dependent cell death pathway. Cell Death Differ. 2003;10(7):850-2. DOI: 10.1038/sj.cdd.440124510.1038/sj.cdd.4401245
Open DOI Search in Google Scholar Back to article
24. Curtin JF, Cotter TG. Live and let die: regulatory mechanisms in Fas-mediated apoptosis. Cell Signal. 2003;15(11):983-92. DOI: 10.1016/S0898-6568(03)00093-710.1016/S0898-6568(03)00093-7
Open DOI Search in Google Scholar Back to article
25. Alenzi FQ. The role of apoptotic proteins in patients with systemic lupus erythematosis. Egypt J Immunol. 2009;16(1):107-16.
Search in Google Scholar Back to article
26. Islam Z, Jahan I, Ahammad RU, Shahnaij M, Nahar S, Mohammad QD. FAS promoter polymorphisms and serum sFas level are associated with increased risk of nerve damage in Banladeshi patients with Guillain-Barre syndrome. Plos One. 2018;12;13(2): e0192703.10.1371/journal.pone.0192703580904629432441
Search in Google Scholar Back to article
27. Leithäuser F, Dhein J, Mechtersheimer G, Koretz K, Brüderlein S, Henne C, et al. Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells. Lab Invest. 1993;69(4):415-29.
Search in Google Scholar Back to article
28. Kim K-M, Lee K, Hong Y-S, Park H-Y. Fas-mediated apoptosis and expression of related genes in human malignant hematopoietic cells. Exp Mol Med. 2000;32(4):246. DOI: 10.1038/emm.2000.4110.1038/emm.2000.4111190279
Open DOI Search in Google Scholar Back to article
29. Asgari R, Mansouri K, Bakhtiari M, Bidmeshkipour A, Yari K, Zadeh FS, Raygani AV. Association of FAS -670 A/G and FASL -844 C/T polymorphisms with idiopathic azospermia in Wertern Iran. Eur J Obstet Gynecol Reprod Biol. 2017; 218: 55-59. DOI: 10.1016/j.ejogrb.2017.09.00310.1016/j.ejogrb.2017.09.00328942044
Open DOI Search in Google Scholar Back to article
30. Park JY, Lee W-K, Jung D-K, Choi J-E, Park T-I, Lee E-B, et al. Polymorphisms in the FAS and FASL Genes and Survival of Early Stage Non–small Cell Lung Cancer. Clin Cancer Res. 2009;15(5):1794-800. DOI: 10.1158/1078-0432.CCR-08-177010.1158/1078-0432.CCR-08-177019240174
Open DOI Search in Google Scholar Back to article

Investigation of the Relation Between FAS, FASLG Polymorphisms and Serum Fas, FasL Levels in Patients with Psoriasis

Abstract

Paradigm

My account