Association of a TNIP1 gene polymorphism with chronic primary immune thrombocytopenia in Chinese population

Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease, characterized by increased platelet destruction and decreased platelet production. Multiple factors have been demonstrated in ITP's pathogenic mechanism, especially genetic polymorphism. Tumor necrosis factor-induced protein 3 (TNFAIP3) gene encodes the ubiquitin-modifying enzyme A20 which limits inflammation by terminating NF-κB. Our previous study demonstrated that TNFAIP3 polymorphisms contributed to the susceptibility of chronic ITP. TNFAIP3 interacting protein 1 (TNIP1), one adaptor molecule binding to A20, is an important inhibiter of NF-κB activity and plays a crucial role in maintaining homeostasis of the immune system. Therefore, we speculated that TNIP1 polymorphisms might be associated with the susceptibility of chronic ITP. We investigated the distribution of TNIP1 polymorphisms in 215 patients with chronic ITP and 200 healthy controls by direct sequencing. We observed significant difference in the allelic (p = 0.01) and genotypic distributions (p = 0.03) of rs7708392 between the ITP and control groups. Further analysis revealed the association of rs7708392 polymorphism with chronic ITP in males as well as in adults. These data suggest an association of TNIP1 polymorphisms with susceptibility to chronic ITP. Our finding indicates that TNIP1 is a shared ITP susceptibility gene. Taken together with the association of TNFAIP3, these observations emphasize the important role of NF-κB regulation in the pathogenesis of ITP.