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Abstract Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder caused by the production of anti-platelet antibodies. These autoantibodies opsonize platelets for splenic clearance, resulting in low levels of circulating platelets. The current case-control study aimed at detecting TNF-Ü (-308 G/A) and TNF-Ý (+252 A/G) genes polymorphism in Egyptian children with chronic ITP to clarify their possible association with chronic evolution of the disease. The current study included 80 chronic ITP patients and 100 matched unrelated healthy controls. Genotyping was performed by using polymerase chain reaction restriction fragment length polymorphism technique (PCR-RFLP). TNF-Ü genotyping revealed that wild G/G, heterozygous G/A and homozygous A/A genotypes among cITP patients were 81.2%, 15% and 3.8% respectively versus 79%, 20% and 1% in the control group, while TNF-Ý genotyping revealed that wild A/A, heterozygous A/G and homozygous G/G genotypes among cITP patients were 55%, 40% and 5% respectively versus 60%, 28% and 12% in the control group, with no statistically significant difference between the two groups. Patients having homozygous genotype of TNF-Ü or TNF-Ý showed higher mean age, longer disease duration & had lower mean platelet count with statistically significant difference from the other genotypes. TNF-Ü polymorphism was more frequent among unresponsive patients compared to responsive patients with statistically significant difference. It was found that patients with combined genes polymorphism had three fold increased risk of development of chronic ITP compared to control group |