The association of CD247 Gene rs858554 and rs704848 Polymorphisms with Immune Thrombocytopenia Disease

Year 2019, , 23 - 27, 30.04.2019

İbrahim Kutlubay Elif Gülsüm Ümit Jülide Tozkır

https://doi.org/10.26650/experimed.2019.19007

Abstract

DOI:
10.26650/experimed.2019.19007

Objective: Immune Thrombocytopenia (ITP) is
a disease characterized by the development of thrombocytopenia as a result of
platelet destruction due to autoantibodies which is against to platelets. There
is the abnormal T cell response that stimulates the proliferation and
differentiation of autoreactive B cells. The first signal is transmitted with
the CD3 zeta chain (CD247) molecule to the T cell for activation. In this
study, the association of immune thrombocytopenia (ITP) disease with rs858554
and rs704848 polymorphisms of CD3 zeta chain (CD247) gene, have been
investigated.

Materials and Methods: The study was
performed with the blood samples taken from 108 donors in the ITP and healthy
control group. The patients with ITP who were followed in Trakya University
Medical Faculty Hematology Clinic were included to the study. The patients and
healthy controls were informed about the study and signed informed consent form
approved by the local ethics committee. The ITP group were including 35
females, 20 males (55 in total) and in the healthy control group there were 31
females, 22 males (53 in total). The allelic variants of rs858554 and rs704848
were determined with “TaqMan
Probe Real-Time PCR”,
the analyses were performed with using “AB Applied Biosystems (SerialNumber: 2720010807)” via VIC/FAM
dyes. The results were statistically evaluated with chi square test.

Results: According to the results of the
study, no significant difference was found in the rs858554 and rs704848
polymorphisms between the ITP group and the healthy control group. Gender
distribution and haplotypic situational analysis, and the clinical finding for
the ITP patients there were no association with allelic and genotypic variants
of polymorphisms.

Conclusion: According to the findings that
the rs858554 and rs704848 polymorphisms did not directly contribute to the
clinical course of ITP disease for the investigated population in this study.

This work was supported by Research Fund of
the Trakya University. Project Number:2017/05

Cite this article as: Kutlubay İ, Ümit EG,
Tozkır J. The association of CD247 gene rs858554 and rs704848 polymorphisms
with Immune Thrombocytopenia Disease. Experimed 2019; 9(1): 23-7.

Keywords

ITP, autoimmunity, immune system, platelet, CD247, polymorphism

CD247 Genine Ait rs858554 ve rs704848 Polimorfizmlerinin İmmün Trombositopeni Hastalığı ile İlişkisi

Abstract

DOI: 10.26650/experimed.2019.19007

Amaç: İmmün trombositopeni (İTP), edinsel
olarak trombositlere karşı gelişen otoantikorlar ve trombopoezde bozulmalar
nedeniyle trombositlerin yıkımı ya da yapım kusuru sonucu trombositopeni gelişimi
ile karakterize bir hastalıktır. Hastalığın patogenezi tam olarak
bilinmemektedir. İTP’de görülen
otoantikorlar genellikle IgG tipinde oluşmaktadır. Bu antikorların oluşumu için
spesifik T hücre klonlarının anormal etkinliği söz konusudur. Bu çalışmada T hücrenin
aktivasyonu için sinyal iletimi yapan CD3 zeta zinciri (CD247) molekülüne ait
rs858554 ve rs704848 polimorfizmleri ile immün trombositopeni (İTP) hastalığının
ilişkisi araştırılmıştır.

Gereç ve Yöntem: Çalışmada İTP’li grupta 35 kadın,
20 erkek verici olmak üzere 55, sağlıklı kontrol grubunda ise 31 kadın, 22
erkek olmak üzere toplam 53 kişi bulunmaktadır. Polimorfik varyantları
belirlemek için TaqMan Probe Real-Time PCR yöntemi kullanılmıştır.

Bulgular: İTP’li hastalar ve sağlıklı kontrol grubu arasında rs858554 ve rs704848
polimorfizmleri açısından anlamlı fark bulunmamıştır. Sonuçlar cinsiyet dağılımına
ve polimorfizmlerin haplotipik dizilimlerine göre değerlendirilmiştir. Gruplar
arasında fark bulunmamıştır. İTP’li hastalar için klinik verileriler açısından yapılan karşılaştırmalarda
anlamlı bir fark belirlenmemiştir.

Sonuç: Elde edilen bulgular ve hastaların klinik
seyrine dair Hematoloji kliniğinden alınan veriler doğrultusunda rs858554 ve
rs704848 polimorfizmlerinin ilgili popülasyon için İTP hastalığının patogenezi
ile doğrudan ilişkili olmadığı tespit edilmiştir.

Bu çalışma Trakya Üniversitesi Bilimsel Araştırma
Projeleri Koordinasyon Birimince Desteklenmiştir. Proje Numarası: 2017/05

Cite this article as: Kutlubay İ, Ümit EG,
Tozkır J. The association of CD247 gene rs858554 and rs704848 polymorphisms
with Immune Thrombocytopenia Disease. Experimed 2019; 9(1): 23-7.

Keywords

İTP, otoimmünite, immün sistem, trombosit, CD247, polimorfizm

References

• 1. Bylsma LC, Fryzek JP, Cetin K, Callaghan F, Bezold C, Mehta B, Wasser JS. Systematicliteraturereview of treatments used for adult immune thrombocytopenia in the second-linesetting. Am J Hematol 2019; 94: 118-32. 2. Neunert CE, Cooper N. Evidence-based management of immune thrombocytopenia: ASH guideline update. Hematology Am Soc Hematol Educ Program 2018; 2018: 568-75. 3. Audia S, Mahévas M, Samson M, Godeau B, Bonnotte B. Pathogenesis of immunethrombocytopenia. Autoimmun Rev 2017; 16: 620-32. 4. Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009; 113: 2386-93. 5. Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA, American Society of Hematology. 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011; 117: 4190-207. 6. Stasi R, Newland AC. ITP: a historical perspective. J Hematol 2011; 153: 437-50. 7. İTP Tanı ve Tedavi Kılavuzu. Türk Hematoloji Derneği, 2011. 8. Grainger JD, Bolton-Maggs PHB, Godeau B, Bussel J, Donato H, Elalfy M, et al. Diagnosis and management of chronic ITP: comments from an ICIS expert group. Ann Hematol 2010; 89: 11-7. 9. Blanchette M, Freedman J. The history of idiopathic thrombocytopenic purpura (ITP). Transfus Sci 1998; 19: 231-6. 10. McMillan R, Luiken GA, Levy R, Yelenosky R, Longmire RL. Antibody against megakaryocytes in idiopathic thrombocytopenic purpura. JAMA 1978; 239: 2460-2. 11. Abbas AK, Lichtman AH. (2nd ed.). (2004). Basic immunology: functions and disorders of the immune system. Phiadelphia, W.B Saunders Co. 12. Ngoenkam J, Schamel WW, Pongcharoen S. Selected signalling proteins recruited to the T-cell receptor-CD3 complex. Immunology 2018; 153: 42-50. 13. Ahonen T, Saltevo J, Laakso M, Kautiainen H, Kumpusalo E, Vanhala M. Gender differences relating to metabolic syndrome and proinflammation in Finnish subjects with elevated blood pressure. Mediators Inflamm 2009; 2009: 959281. 14. Degner JF, Pai AA, Pique-Regi R, Veyrieras JB, Gaffney DJ, Pickrell JK, et al. DNase I sensitivity QTLs are a majör determinant of human expression variation. Nature 2012; 482: 390-4. 15. Trynka G, Sandor C, Han B, Xu H, Stranger BE, Liu XS, et al. Chromatin marks identify critical cell types for fine mapping complex trait variants. Nature Genetics 2013; 45: 124-30. 16. Zhang CM, Yu LY, Lv JF, Gong L, Zhou HH, Chen XP, et al. Effects of immuno-related gene polymorphisms on a bispecific antibody targeting colorectal cancer cell. Per Med 2018 15: 167-79. 17. Li P, Wang X, Zhao MQ, Li LJ, Zhang C, Li BZ, et al. TCR-CD3ζ gene polymorphisms and expression profile in rheumatoid arthritis. Autoimmunity 2016; 49: 466-71. 18. Martins M, Williams AH, Comeau M, Marion M, Ziegler JT, Freedman BI, et al. Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study. Genes Immun 2015; 16: 142-50.