Association of dopamine β-hydroxylase polymorphism rs1611115 and serum levels with psychiatric disorders in Pakistani population

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.

Keywords:

• Dopamine beta-hydroxylase
• DBH serum levels
• bipolar disorder
• depression
• Schizophrenia

Acknowledgements

We thank all the subjects for their cooperation and participation in the study. We are also grateful to the Pakistan Institute of Medical Sciences (PIMS) hospital Islamabad and the staff members for their valuable support in sample collection.

Declarations

Availability of data and materials

All the data is mentioned in the manuscript and the rest of the data is mentioned as supplementary data in an additional file which will be available with the manuscript.

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

The current study conforms to the Helsinki Declaration and was approved by the Ethics Review Board of the Department of Biosciences, COMSATS University Islamabad, Pakistan. All the participants were informed about the purpose of the study and informed consent was attained from all the participants. The privacy rights of all the participants were preserved by anonymizing the relevant data.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The study was supported by the Higher Education Commission of Pakistan (grant no. 3738), given to Maleeha Azam and the Pakistan Academy of Sciences (grant no. 5-9/PAAS/1082) given to Raheel Qamar. This research was supported by COMSATS University Islamabad (CUI), Pakistan core grant to Raheel Qamar.