Combined tumor necrosis factor-α (-308 G/A) and tumor necrosis factor-β (+252 A/G) nucleotide polymorphisms and chronicity in Egyptian children with immune thrombocytopenia

Background Primary immune thrombocytopenia (ITP) is a common autoimmune disorder. Secretion of TNF-alpha, TNF-beta and IFN-gamma plays a major role in the pathogenesis of ITP.Objective This cross-sectional study aimed to detect TNF-alpha (-308 G/A) and TNF-beta (+ 252 A/G) gene polymorphism in a cohort of Egyptian children with chronic ITP (cITP) to clarify their possible association with progression to chronic disease.Methods The study included 80 Egyptian cITP patients and 100 unrelated age-and sex-matched controls. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results Patients with TNF-alpha homozygous (A/A) genotype had significantly higher mean age, longer disease duration and lower platelet counts (p values 0.005, 0.024 and 0.008, respectively). TNF-alpha wild (G/G) genotype was significantly more frequent among responders (p = 0.049). Complete response was more frequent among wild (A/A) TNF-beta genotype patients (p = 0.011), and platelet count was significantly lower among homozygous (G/G) genotype (p = 0.018) patients. Combined polymorphisms were strongly associated with susceptibility to chronic ITP.Conclusion Homozygosity in either gene might contribute to a worse course of disease, increased severity and poor response to therapy. Patients expressing combined polymorphisms are more prone to progression to chronic disease, severe thrombo-cytopenia and longer disease duration.