The Transcriptional Activity Of Interleukin18Gene(IL18) Promoter Polymorphisms In Alzheimer’s Disease

Background: Alzheimer’s disease is an neuronal degenerativedisorder that is mainly characterized by progressive dementia in the old.Although etiology is not clear, numerous studies demonstrate that itis related to the chronic inflammatory response in brain. As ainflammatory cytokine, IL18has been confirmed to relate with AD. SNPSincluding－607C/A （RS1946518）、－137G/C（RS187238）exist in IL18generegulatory region. The relationship between SNPSand AD have beenreported,but so far, SNPSin the promoter region affect IL18promotoractivity that haven’t been reported.Objective:Through molecular biological technique, construct IL18－607C/A、IL18－137G/C wild-type and mutant-type pGL4.10vector.Theeffort of－607C/A、－137G/C polymorphism on promoter activity have beenresearched at cell line.Method: We selected the Dual-Luciferase reporter assay system(pGL4.10(luc2) Basic and pRL-TK) as carrier, and used the geneticrecombination and site-directed mutagenesis methods to build reporter gene plasmids of IL18,then transient transfected into the HEK293cells.The relative luciferase activity (RLA) was calculated to explore the roleof different SNPs on transcriptional activities of different promoters.Result: All IL18promotor plasmids were found to have clear promoteractivity; there were significant differences in promoter activity betweenthe mutational plasmids and the wild plasmid（P<0.01）, but two-sitemutational plasmid had lower activity than the singal mutational ones（P>0.05）.Conclusions: The variation of-607A/C and-137G/C could influencethe transcriptional activity of IL18gene, all mutational plasmids couldraise the transcriptional activity, therefore, the expression of proteinIL18could be elevated which may play an important role in theneuroinflammation pathogenesis of AD.