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 association of DBH functional polymorphism rs1611115 and its effect on DBH levels in serum in major depressive disorder (MDD), bipolar disorder (BPD) and schizophrenia (SHZ) in the Pakistani population. In total n = 1097 subjects including MDD (n = 427), BPD (n = 204), SHZ (n = 134) and healthy controls (n = 332), were screened for rs1611115 by polymerase chain reaction-restriction fragment length polymorphism. Univariate logistic regression was applied and results were adjusted for age and sex (multivariant analysis). The DBH levels in serum were determined through enzyme-linked immunosorbent assay (ELISA) and the Mann Whitney U test was applied. The results showed a signi cant association of minor allele (-1021C > T) with a higher risk of developing BPD and SHZ in both univariable and multivariable analyses. Moreover, 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 BPD group. Thus the present study suggested a signi cant association of DBH rs1611115 with BPD and SHZ and also the effect of rs1611115 on DBH serum levels in MDD and BPD, for the rst time in the Pakistani population.

The dopaminergic pathways control neural signals that modulate mood and behaviour along and have a vital role in the aetiology of major depression (MDD), schizophrenia (SHZ) and bipolar disorder (BD). Genome-wide association studies (GWAS) have reported several dopaminergic pathway’s and other genetic loci’s association with these disorders, therefore, the present study was conducted to analyse the GWAS and candidate gene loci of the dopaminergic and cognitive system genes in MDD, SHZ, and BD, in the Pakistani population. A total of 1237 subjects [MDD n = 479; BD n = 222; SHZ n = 146; and controls n = 390], were screened for eleven genetic variants through polymerase chain reaction (PCR) techniques. Univariant followed by multivariant logistic regression analysis were applied to determine the genetic association. Significant risk associations were observed for rs4532 and rs1799732 with MDD; and rs1006737 and rs2238056 with BD. However, after applying multiple test corrections rs4532 and rs1799732 association did not remain significant for MDD. Moreover, a protective association was found for three variants DRD4-120bp, rs10033951 and rs2388334 in the current cohort. Thus, in conclusion, the current study revealed the risk association of rs1006737 and rs2238056 with BD and the protective effect of DRD4-120bp in MDD and BD, of rs2388334 in BD and of rs10033951 in MDD, BD, and SHZ in the current Pakistani cohort.

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 association of DBH functional polymorphism rs1611115 and its effect on DBH levels in serum in major depressive disorder (MDD), bipolar disorder (BPD) and schizophrenia (SHZ) in the Pakistani population. In total n = 1097 subjects including MDD (n = 427), BPD (n = 204), SHZ (n = 134) and healthy controls (n = 332), were screened for rs1611115 by polymerase chain reaction-restriction fragment length polymorphism. Univariate logistic regression was applied and results were adjusted for age and sex (multivariant analysis). The DBH levels in serum were determined through enzyme-linked immunosorbent assay (ELISA) and the Mann Whitney U test was applied. The results showed a significant association of minor allele (-1021C > T) with a higher risk of developing BPD and SHZ in both univariable and multivariable analyses. Moreover, 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 BPD group. Thus the present study suggested a significant association of DBH rs1611115 with BPD and SHZ and also the effect of rs1611115 on DBH serum levels in MDD and BPD, for the first time in the Pakistani population.