Abstract:
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 (ARMSPCR).
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.
