Impact The5-HTR_2A-1438A/G（Rs6311） Polymorphism In Serotonin2A Receptor On Promoter Activity

Background The pathogenesis of mental disorders is not yet clear, many scholars have proposed causes many neurotransmitter hypothesis. Hyperfunction hypothesis such as dopamine, glutamate hypothesis, the most important of which is5-serotonin (5-HT) hypothesis. The people found in the central nervous system in the presence of5-HT abnormalities evidence from cerebrospinal fluid, platelet, neural structure and its metabolites different research directions.5-HT important neurotransmitter involved in the synthesis of tryptophan, and direct or indirect contact with a lot of mental illness symptoms, but research also shows that both5-serotonin and its major metabolite5-hydroxyindoleacetic acid in the cerebrospinal fluid level, to better reflect the brain-serotonin transmission. Regulating activity through its multiple receptors play an important neurotransmitter5-HT in the nervous system, such as mood, feeding, learning, impulsivity, memory, sexual behavior and cognition.Dysfunction of5-HT and5-HT receptor function missing that a major cause of mental disorders. Fourteen kinds cloned5-HT neurotransmitter receptors and are classified into seven type. Studies have shown that5-HTR2A frontal suicide in front of a crowd of mental disorders express the amount of studies have shown that the number of receptors down. That the5-HTR.2A loss of function in the brain is one of the causes of mental disease.Objective To investigate the effect of5-HTR2A-1438A/G (rs6311) polymorphism on promoter activity have been research at Hela and IMR-32cell lines.Methods5-HTR2A gene of human was got by RT-PCR.5-HTR2A gene and plasmid TK-PGL were both digested by enzymes, the digestion fragments were ligated to construct exprimental vectors-1438A-TK-PGL4.17and-1438G-TK-PGL4.17.The constructed plasmids were transfected into Hela cell line and IMR-32cell line. After cultrue48h, the enzymatic activity and the sensitivity of the cells examinated with dual luciferase reportor assay. Western Blotting was used to detect the levels of5-HTR.2A protein at site-1438A/G polymorphism in Hela and IMR-32cell lines.Results Hela cell line5-HTR2A-1438A/A (rs6311) can effect promotor activity.5-HTR2A-1438A/A (rs6311) wild genotypeshave a higher activity than5-HTR2A-1438G/G (rs6311) mutant genotypc(P<0.05), on the contrary, IMR-32cells5-HTR2A-1438A/A (rs6311) wild genotype and5-HTR2A-1438G/G(rs6311) mutant genotype have no statistical significant(P>0.05) on promoter activity. Western blotting demonstrated that the5-HTR2A protein was higher that in Hela cells and did not significantly in IMR-32cells.Conclusions The5-HTR2A-1438A/G has the potential to modulate5-HTR2A promoter activity in vitro.