Impact Of The -783A/G Polymorphism In Serotonin 2A Receptor Gene On Promoter Activity

Background:Atypical Antipsychotics have been used widely all over the world,5-HT2AR is the main target of the Atypical Antipsychotics. The HTR2A-1438A/G might be a functional SNP that affects promoter activity, the presence of the A allele significantly increases the promoter activity; and-1438G/G can lead to 5-HT2AR down-regulation, this relevant to schizophrenia. But so far, The-783A/G polymorphism in the high promotor activity region affect 5-HT2AR promotor activity that havn't been reported.Objective:Through molecular biological technique, constructe 5-HT2AR-783A/G wild-type and mutant-type TK-PGL4.17 vector. The effect of 5-HT2AR-783A/G polymorphism on promoter activity have been research at two cell lines.Method:We use TK-PGL4.17 vector that containe low level express HSV-TK promoter to construct exprimental vectors TK-PGL4.17-5-HT2AR-783A/A-and TK-PGL4.17-5-HT2AR-783G/G, use PRL-TK as internal vector. Through cultrue 48h, dual luciferase reportor assay examinated after contransfect exprimental vectors and PRL-TK to Hela and IMR-32 cell lines.Result:At hela cells 5-HT2AR-783A/A can effect promotor activity.-783A/A wild genotypes (101.60±39.24) have a higher activity than-783G/G mutant genotype(46.59±25.37, P＜0.05); but at IMR-32 cells-783A/A wild genotype(7.57±3.32) and-783G/G mutant genotype (6.38±4.37)have no statistical significant (P>0.05) on promoter activity.Conclusions:The 5-HT2AR-783A/G has the potential to modulate HTR2A promoter activity, and is the functional variant responsible for shizophrenia.