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    Major depressive disorder (MDD) is characterized as clinical depression, which primarily affects the mood and behaviour of an individual. In the present study butyrylcholinesterase (BChE), a co-regulatory cholinergic neurotransmitter enzyme implicated in several putative neuronal and non-neuronal physiological roles was investigated for its role in MDD. Eighty MDD patients and sixty-one healthy controls were recruited for the study. BChE activity was measured by Ellman's method using serum while DNA samples of the patients were genotyped for BCHE polymorphisms rs3495 (c.*189G > A) and rs1803274 (c.1699G > A) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and tetra-primer Amplification Refractory Mutation System- polymerase chain reaction (ARMS-PCR). The genotyping was further validated by Sanger Sequencing. Biochemical estimation of serum BChE levels revealed a statistically significant decrease of enzyme activity in MDD patients (69.96) as compared to healthy controls (90.97), which was independent of age and gender. BCHE single nucleotide polymorphism rs1803274 genotype GA was found to be associated with the disease under a dominant model (OR 2.32; 95% CI 1.09-4.96; p value = 0.025). Furthermore, risk allele-A frequency was higher in cases (p value = 0.013) than control. Carriers of rs1803274 GA genotype showed reduced mean BChE activity than wild-type allele GG homozygotes (p value = 0.040). Gender-based analysis revealed a protective role of rs3495 in females (χ2 = 6.87, p value = 0.032, RM: OR 0.173, CI = 0.043-0.699 (p value = 0.017). In addition, rs1803274 risk allele-A was observed to be significantly higher in males (χ2 = 4.258, p value = 0.039). In conclusion, the present study is indicative of a role of BChE in the pathophysiology of MDD where genetic polymorphisms were observed to effect BChE activity. Further replication studies in different ethnicities are recommended to validate the current observations. © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.


    Sliha Awan, Aisha N Hashmi, Rizwan Taj, Sadaf Munir, Rabia Habib, Sajida Batool, Maleeha Azam, Raheel Qamar, Syed M Nurulain. Genetic Association of Butyrylcholinesterase with Major Depressive Disorder. Biochemical genetics. 2022 Apr;60(2):720-737

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    PMID: 34414522

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