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

Abstract

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.

ExploringWNT2Polymorphisms in Comitant Strabismus: A Genetic Association Study

“…We compared allele frequencies of the studied control cohort to the PJL dataset from the 1000 Genomes project and found significant differences for three of the variants i.e., rs2896218, rs3779550 and rs2024233. Hashmi et al, (2022) 44 and Khan et al, (2020) 42 from our research group reported similar observations, one reason for this could be that the majority of the samples collected for this and the previous studies were from the twin cities of Rawalpindi and Islamabad. Both these cities comprise people from diverse backgrounds including a high influx of Pashtuns from Khyber Pakhtunkhwa.…”