Abstract:
Aim: Dopamine β-hydroxylase (DBH) is a copper-containing enzyme that has an important role
in maintaining the cellular homeostasis between the two neurotransmitters, dopamine (DA) and
nor-adrenaline (NA). DBH functional polymorphisms are associated with multiple neuro-psychiatric
conditions and are found to alter the DBH protein levels in serum affecting DBH enzymatic
activity. The current study was conducted to determine the genetic and serum levels association
of DBH rs1611115 functional polymorphism with major depressive disorder (MDD), bipolar
disorder (BD) and schizophrenia (SHZ) in the Pakistani population.
Methods: In total n = 1097 subjects including MDD (n = 427), BD (n = 204), SHZ (n = 134) and
healthy controls (n = 332), were screened for the functional polymorphism by polymerase chain
reaction-restriction fragment length polymorphism. Univariate logistic regression analysis was
applied and the results were adjusted for age and sex. The DBH levels in serum were determined
through enzyme-linked immunosorbent assay (ELISA) and the Mann Whitney U test was applied.
Results: The minor allele (-1021 C > T ) was found to be significantly associated with a higher risk
of developing BD and SHZ in both univariable and multivariable analyses. The overall total
serum concentration of DBH was comparatively raised in MDD, however, in cross-comparison
DBH serum levels were found markedly higher in CC homozygotes compared to TT homozygotes
within the BD group.
Conclusion: The present study suggested a significant association of DBH rs1611115 with BD
and SHZ and also the effect of rs1611115 on DBH serum levels in MDD and BD for the first
time in the Pakistani population.
