宿主遗传背景对H.pylori感染者的临床转归具有重要影响。CagA+H.pylori菌株感染后与宿主细胞应答基因PTPN11直接结合形成复合体，引发细胞生物学效应。我们前期实验研究及生物信息学预测提示，PTPN11rs12229892G→A改变可能影响PTPN11基因选择性剪接，产生具有截短PTP结构域的变异剪接体，影响其与H.pyloriCagA相互作用的生物学效应。PTPN11变异剪接体是否降低原有的磷酸酶活性，失去ERK1/2激活及STAT3抑制作用，活化STAT3/BMP2/SMAD1通路诱导胃黏膜肠上皮化生，进而引起生物学效应表型的变化目前尚不清楚。本研究采用细胞培养、实验动物及人体组织标本，从体内外多角度研究PTPN11剪接变异体与H.pyloriCagA的互作效应及分子机制，旨在阐明H.pyloriCagA对靶向人群的致病作用及机制，为其精准治疗提供理论依据及研究基础。

The genetic background of the host has an important impact on the clinical outcome of H. pylori infection. After infection with CagA + H. pylori strain, the host cell response gene PTPN11 directly binds with CagA to form a complex, which leads to cell biological effects. Our previous experimental studies and bioinformatic predictions suggest that the G → A alteration of PTPN11 rs12229892 may affect the alternative splicing of PTPN11 gene and produce a mutant spliced variant with a truncated PTP domain that affects its interaction with H. pylori CagA and its biology effect. It is not clear whether the PTPN11 mutant spliceosome reduces the original activity of phosphatase, loses ERK1 / 2 activation and STAT3 inhibition, and activates the STAT3 / BMP2 / SMAD1 pathway to induce gastric mucosal intestinal metaplasia, leading to changes in the biological phenotype. In this study, cell culture, laboratory animals and human tissue samples were used to investigate the interaction and molecular mechanisms of PTPN11 splicing variants and H. pylori CagA, from multiple perspectives including in vitro and in vivo. We aimed at elucidating the pathogenesis and mechanism of H. pylori CagA for target population, to provide the theoretical basis and research foundation for its precise treatment.