Impact of TNFAIP3 Genetic Polymorphisms on Primary Immune Thrombocytopenia in Egyptian Adults: Case-control Study


  • Mohamed Zanaty Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt
  • Osama Korayem Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt
  • Mohamed H. Meabed Department of Pediatrics, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
  • Doaa El Demerdash Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
  • Wafaa M. Abdelghany Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt



Immune thrombocytopenia, TNFAIP3, Linkage disequilibrium, Susceptibility, Prognosis


BACKGROUND: Immune Thrombocytopenia (ITP) is a common acquired hematological disease. Genetic polymorphisms play an important role in ITP pathogenesis and prognosis. TNF-α-induced protein 3 (TNFAIP3) is a negative regulator of NF-kB in many signaling pathways. Several variants of TNFAIP3 have been associated with various inflammatory autoimmune disorders.

AIM: Our study aimed to study the association of TNFAIP3 single nucleotide polymorphisms (SNPs); rs2230926 & rs5029939 with ITP susceptibility, as well ITP prognosis by follow up the cases for 18 months.

METHODS: One hundred and ten ITP patients as well 110 matched unrelated normal controls were enrolled in our study. The polymorphisms were assessed by real-time polymerase chain reaction (real time PCR).

RESULTS: There were a significant difference between cases and control groups regarding rs2230926 T>G and rs5029939 C>G frequencies with p < 0.05. Linkage disequilibrium (LD) analysis of the two variants revealed that there was a significant LD (p < 0.001). Non-cutaneous bleeding manifestations were observed mainly in the mutant genotypes of rs2230926 and rs5029939. The ITP patients with mutant genotypes of rs5029939 showed more need to use 2nd line immunosuppressive therapy as well the mutant genotypes of rs2230926 showed more steroid dependence and less complete recovery.

CONCLUSION: Our data concluded the presence of LD between rs5029939 and rs2230926. The mutant genotypes of both variants were associated with increase the susceptibility to ITP and accompanied by worse clinical manifestations and poor response to the treatment in the adult Egyptian patients.


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Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017;129(21):2829-35. PMid:28416506 DOI:

Khodadi E, Asnafi AA, Shahrabi S, et al. Bone marrow niche in immune thrombocytopenia: A focus on megakaryopoiesis. Ann Hematol. 2016;95(11):1765-76. PMid:27236577 DOI:

Zufferey A, Kapur R, Semple JW. Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP). J Clin Med. 2017;6(2):16. PMid:28208757 DOI:

Cines DB, Bussel JB, Liebman HA, Prak ET. The ITP syndrome: Pathogenic and clinical diversity. Blood. 2009;113(26):6511-21. PMid:19395674 DOI:

Goubran H, Hart C, Othman I, Seghatchian J. Flow cytometry and immune thrombocytopenic purpura. Trans Apher Sci. 2018;57(6):800-3. DOI:

Xuan M, Li H, Fu R, Yang Y, Zhang D, Zhang X, et al. Association of ABCB1 gene polymorphisms and haplotypes with therapeutic efficacy of glucocorticoids in Chinese patients with immune thrombocytopenia. Hum Immunol. 2014;75(4):317-21. PMid:24486577 DOI:

Rasi S, Rossi D, Gaidano G. TNFAIP3 (tumor necrosis factor, alpha-induced protein 3). Atlas Genet Cytogenet Oncol Haematol. 2010;5:488-92. DOI:

Zhao H, Wang L, Luo H, Li QZ, Zuo X. TNFAIP3 downregulation mediated by histone modification contributes to T-cell dysfunction in systemic lupus erythematosus. Rheumatology. 2017;56(5):835-43. PMid:28158872 DOI:

Matsuzawa Y, Oshima S, Takahara M, Maeyashiki C, Nemoto Y, Kobayashi M, et al. TNFAIP3 promotes survival of CD4 T cells by restricting MTOR and promoting autophagy. Autophagy. 2015;11(7):1052-62. PMid:26043155 DOI:

Zhou H, Yang J, Liu L, Zhang D, Zhou K, Li H, et al. The polymorphisms of tumor necrosis factor-induced protein 3 gene may contribute to the susceptibility of chronic primary immune thrombocytopenia in Chinese population. Platelets. 2016;27(1):26-31. PMid:25806576 DOI:

Musone SL, Taylor KE, Lu TT, Nititham J, Ferreira RC, Ortmann W, et al. Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet. 2008;40(9):1062-4. PMid:19165919 DOI:

Adrianto I, Wen F, Templeton A, Wiley G, King JB, Lessard CJ, et al. Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus. Nat Genet. 2011;43(3):253-8. PMid:21336280 DOI:

Bates JS, Lessard CJ, Leon JM, Nguyen T, Battiest LJ, Rodgers J, et al. Meta-analysis and imputation identifies a 109 kb risk haplotype spanning TNFAIP3 associated with lupus nephritis and hematologic manifestations. Genes Immun. 2009;10(5):470-7. PMid:19387456 DOI:

Ciccacci C, Latini A, Perricone C, Conigliaro P, Colafrancesco S, Ceccarelli F, et al. TNFAIP3 gene polymorphisms in three common autoimmune diseases: Systemic lupus erythematosus, rheumatoid arthritis, and primary Sjogren syndrome-association with disease susceptibility and clinical phenotypes in Italian patients. J Immunol Res 2019;2019:6728694. PMid:31534975 DOI:

Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther MA. The American society of hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-207. PMid:21325604 DOI:

Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, 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(11):2386-93. PMid:19005182 DOI:

Berger S, Schlather M, de los Campos G, Weigend S, Preisinger R, Erbe M, et al. A scale-corrected comparison of linkage disequilibrium levels between genic and non-genic regions. PLoS One. 2015;10(10):e0141216. PMid:26517830 DOI:

Swinkels M, Rijkers M, Voorberg J, Vidarsson G, Leebeek FW, Jansen AJ. Emerging concepts in immune thrombocytopenia. Front Immunol. 2018;9:880. PMid:29760702 DOI:

Vereecke L, Beyaert R, van Loo G. Genetic relationships between A20/TNFAIP3, chronic inflammation and autoimmune disease. Biochem Soc Trans. 2011;39(4):1086-91. PMid:21787353 DOI:

Ma A, Malynn BA. A20: Linking a complex regulator of ubiquitylation to immunity and human disease. Nat Rev Immunol. 2012;12(11):774-85. Mid:23059429 DOI:

Kool M, Van Loo G, Waelput W, De Prijck S, Muskens F, Sze M, et al. The ubiquitin-editing protein a20 prevents dendritic cell activation, recognition of apoptotic cells, and systemic autoimmunity. Immunity. 2011;35(1):82-96. PMid:21723156 DOI:

Broen JC, Coenen MJ, Radstake TR. Genetics of systemic sclerosis: An update. Curr Rheumatol Rep. 2012;14(1):11-21. Mid:22102179 DOI:

Abd El-Hady M, Mosallam DS, Anis K, Mansour BS, Yassa ME. Tumor necrosis factor induced protein 3 gene polymorphism and the susceptibility to chronic primary immune thrombocytopenia in Egyptian children: A case-control study. Egypt J Med Hum Genet 2021;22(12):1-9. DOI:




How to Cite

Zanaty M, Korayem O, Meabed MH, El Demerdash D, Abdelghany WM. Impact of TNFAIP3 Genetic Polymorphisms on Primary Immune Thrombocytopenia in Egyptian Adults: Case-control Study. Open Access Maced J Med Sci [Internet]. 2022 Jan. 2 [cited 2023 Mar. 31];10(A):525-30. Available from: