BackgroundImmune Thrombocytopenia (ITP) is a relatively common acquired hematological disorder, affecting 2 to 4/100000 adults. Understanding of the pathogenesis of ITP has been greatly improved with taking into consideration the important role of the genetic variants. This study aimed at investigating the incidence of TNFAIP3 SNPs (rs2230926 and rs5029939) in primary ITP Egyptian patients as well as their response to therapy in addition to the linkage between the two SNPs.Methods and Resultsthe study was conducted in 110 ITP patients diagnosed as primary ITP (PITP) selected among cases referred to the Hematology Outpatient Clinic of Kasr El Aini Hospital and 110 matched healthy controls. The polymorphisms were detected by real-time polymerase chain reaction (real-time PCR). Data indicated that there is a significant difference in the allelic distribution between PITP patients and the control group regarding rs2230926 and rs5029939 (p-value <0.05). Regarding LD analysis of the two SNPs, it has been revealed that there was a significant linkage disequilibrium between rs2230926 and rs5029939 among PITP group LD (D' = 0.966, r2 = 0.694, p-value < 0.001). On behalf of improvement by treatment, patients with rs2230926 wild genotype showed a more significant response to treatment than mutant type (p-value <0.05).ConclusionThere was a correlation between TNFAIP3 SNPs (rs2230926 and rs5029939) and the occurrence of primary ITP in the adult Egyptian populations and there was a linkage disequilibrium between them. Moreover, patients with rs2230926 wild genotype showed significant improvement than mutant type.

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.

Background and Objectives: Myeloproliferative neoplasms (MPNs) are Philadelphia negative disorders involving polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF). Although JAK2 mutation is almost involved, other several mutations are linked to MPNs risk and prognosis. TNFAIP3 genetic mutations are related to several cancers and autoimmune diseases. Our study aimed to demonstrate the effects of rs2230926_T/G & rs5029939_C/G SNVs of TNFAIP3 gene on the risk and prognosis of JAK2 V617F positive MPNs. Methods: Matched 2 groups in age, sex and race were enrolled in our research; 80 MPNs cases group and 130 normal healthy controls group with follow up of MPNs cases for 3 years.  Taqman assay probes involved in real time polymerase chain reaction (PCR) were utilized for variants analysis. Results: The rs2230926 & rs5029939 SNVs were in modest linkage disequilibrium (LD) in MPNs cases. The observed frequencies of G allele and its genotypes of both variants were more prevalent in MPNs patients than normal controls. The bleeding symptoms and the presence of splenomegaly were more existent in the heterozygous genotype and the combined G involved genotypes respectively. The overall survival (OS) was lower in G containing genotypes of both variants but the progression free survival (PFS) was affected only in rs5029939 SNV. Conclusion: Our study revealed the association of G containing genotypes of both rs2230926 & rs5029939 SNVs to the increased MPNs incidence as well to poor clinical course and prognosis of JAK2 V617F positive MPNs disorders in Egyptian ethnic.

BACKGROUND: Chronic myeloid leukemia (CML) is one of the most common hematological tumors. Gene candidate studies cleared the association of single genetic variants (SNVs) to the risk and progression in CML. MicroRNA biogenesis genes disruption contributes a fundamental role in carcinogenesis. AIM: We aimed to determine the association between rs636832 and rs2740348 SNVs of AGO1 gene and GEMIN4 gene, respectively, and the risk and prognosis in CML Egyptian patients with 5 years survival estimation. METHODS: The study was conducted on 110 newly diagnosed CML patients and 110 age and sex healthy matched controls. Real-time polymerase chain reaction utilizing TaqMan probes was operated to demonstrate genetic modalities of rs636832 and rs2740348. RESULTS: No significance difference was observed between the cases and controls regarding the genotypic and allelic frequencies for both variants. On the other hand, the rs636832 GG genotype was more evident at a younger age of diagnosis and associated with the poor grades of the Sokal and Eutos scores. As well, rs2740348 CC genotype was encountered in high Eutos score levels. Regarding the response therapy, rs636832 GG genotype was overrepresented in the resistance to Imatinib while rs2740348 CC genotype was prevalent in the resistance to both Imatinib and Nilotinib. Overall survival was of no statistical significance for both variants. CONCLUSION: Our study revealed that the major homozygous genotypes of both variants were associated with bad prognostic clinical scores and poor response to therapy but with no role in CML risk.

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