NEUROPHARMACOLOGICAL IMPLICATIONS OF COMT GENE VARIANTS ON DOPAMINERGIC FUNCTION IN THE INDIAN POPULATION

Background: Catechol-O-methyltransferase (COMT) is a key enzyme involved in dopamine metabolism in the brain. Genetic variation in the COMT gene, particularly the rs4680 (Val158Met) polymorphism, alters enzyme activity and influences dopamine availability in the prefrontal cortex. These differences can affect cognition, emotional regulation, stress response, and sensitivity to neuropsychiatric medications. Given India’s high genetic diversity, population-specific evaluation of COMT variants is essential for personalized neuropharmacology. Objectives: To examine the functional and neurophysiological impact of common COMT gene polymorphisms in the Indian population using bioinformatic and simulation-based approaches. Methods: An in-silico descriptive study was conducted using allele frequency data from the IndiGenomes database. Five functionally relevant COMT variants (rs4680, rs4633, rs6269, rs4818, and rs737865) were analyzed. Functional effects were assessed using established computational prediction tools. Genotype frequencies were simulated in a hypothetical Indian cohort of 1,000 individuals based on Hardy–Weinberg equilibrium to infer dopamine tone and predicted drug response patterns. Results: The analysis demonstrated marked interindividual variability in COMT activity and predicted dopamine levels. Variants associated with reduced COMT function were linked to higher prefrontal dopamine availability, while regulatory variants influenced enzyme expression and dopamine turnover. These genetic differences translated into distinct predicted responses to stimulants, antidepressants, and antipsychotics. Conclusion: COMT polymorphisms significantly influence dopaminergic balance and neuropharmacological response in the Indian population. These findings support the potential utility of COMT genotyping in guiding personalized treatment strategies in psychiatry and neurology.