To Explore The Association Of Dopamine Beta-Hydroxylase (DBH) Polymorphism And RUNX1 Transcription Factor With The Activity And Function Of Alcohol Use Disorders (AUD)

Objective: To investigate the effect of AUD-related rs1611115 polymorphism on DBH gene expression and enzyme activity.To further verify the effect of DBH expression on norepinephrine secretion.Methods: The dual-luciferase reporter vector of DBH promoter was constructed,and the regulation of rs1611115 polymorphism on DBH gene expression level was studied by dual-luciferase reporter experiment.To predict the transcription factor RUNX1(Runt-related transcription factor 1,Runt-related transcription factor 1),establish the recombinant therapy of RUNX1 overexpression,and transfect HEPG2 cells to further verify its transcriptional regulation on DBH,the expression level of DBH protein and the level of norepinephrine secretion were determined.Results:(1)Dual luciferase activity: the promoter activity of wild-type DBH-WT(TT genotype)was significantly lower than that of mutant DBH-MUT(CC genotype)(p < 0.05).The promoter activity of wild-type RUNX1 overexpression group was significantly higher than that of no-expression group(p < 0.05).(2)The expression and norepinephrine level of DBH protein in the RUNX1 overexpression group were significantly higher than those in the control group(p < 0.05).Conclusion: The polymorphism of DBH rs1611115 is associated with DBH activity,and the activity of CC genotype is higher than that of TT genotype,increase the function of norepinephrine secretion.