白细胞介素-1β基因多态性与慢性萎缩性胃炎基因表达谱的变化

Interleukin-1 beta gene polymorphisms and variation in whole genomic expression profiles of chronic atrophic gastritis

目的应用寡核苷酸基因芯片技术，研究白细胞介素（IL）-1β—31CC／-51ITT基因型慢性萎缩性胃炎全基因表达谱。方法选择IL-1β-31CC／-511TT及IL-1β-31TT／-511CC基因型慢性萎缩性胃炎各6例，留取胃窦胃镜活检组织抽提RNA，应用Agilent人全基因表达谱芯片进行检测，比较两种基因型的慢性萎缩性胃炎基因表达谱，筛选IL-1β—31CC／-511TT基因型相关差异基因，并进一步进行Gene Ontology（GO）分析。结果与IL-1β-31CC／-511TT基因型相关差异基因共有200个，上调159个，下调41个。差异基因主要涉及大分子代谢、翻译后蛋白修饰、泛素循环、蛋白激酶级联反应等。可能最具生物学活性的基因包括下调基因蛋白原转化酶枯草杆菌蛋白酶5，上调基因蛋白激酶C的alpha亚型、核蛋白定位4同源物、毛球族同源物3、人促分裂素原活化蛋白激酶激活的蛋白激酶3等。结论IL-1β-31CC／-511TT基因型慢性萎缩性胃炎具有更多肿瘤、炎症相关的分子表型，这类慢性萎缩性胃炎更需重视干预治疗和动态监测。

Objective To investigate the whole genomic expression profiles of chronic atrophic gastritis with interleukin （ IL）-1β-31CC/-511TT genotype as measured by oligonucleotide microarray technique. Methods Genomic RNA was extracted from gastric biopsies of 12 patients with chronic atrophic gastritis （6 with IL-1β-31CC/-511TT and 6 with IL-1β-31TT/-511CC）. The genomic profiles of IL-1β gene polymorphisms 31CC/-511TT and 31TT/-511CC were compared and tested for differential expressed genes associated with 31CC/-511TT using Agilent human whole genomic oligonucleotide microarrays. The results were further analyzed in terms of gene ontology （GO）. Results There were 200 differentially expressed genes associated with IL-1β-31CC/-511TT, 159 of which were up-regulated and 41 were down-regulated. These genes mainly involved in macromolecule metabolic process, post-translational protein modification, ubiquitin cycle, and protein kinase cascade. Five genes had biological activities,one of which was down-regulated gene （PCSKS） and 4 were upregulated genes （PRKCA, NPLOC4, TRIB3 and MAPKAPK3）. Conclusions The chronic atrophic gastritis with IL-1β-31CC/-511TT genotype has molecular phenotypes Which is associated with malignance and inflammation. These individuals are needed more intensive preemptive treatment and dynamic surveillance.