DNA SEQUENCING, MUTATIONAL ANALYSIS OF NOVEL COMT GENE VARIANTS AND ITS PATHOGENICITY IN SCHIZOPHRENIA PATIENTS: ACROSS-SECTIONAL STUDY FROM TUMKUR DISTRICT OF SOUTH KARNATAKA

Introduction: Schizophrenia is a multi-factorial neuropsychiatric disorder, influenced by environmental and genetic factors. The catechol-O-methyltransferase (COMT) gene is a crucial for the metabolism of dopamine. It has been thoroughly investigated for its potential role in SCZ. At the same time; several variants in the COMT gene have been reported in diverse populations in South Karnataka but remain unexplored. Aim: To assess the novel variants related to the COMT gene and their correlation with SCZ symptoms and other health issues in patients. Materials and Methods: The study was carried out on 80 patients aged between 18 and 60 years; the results were compared with healthy controls of 80. The samples of blood were collected for the DNA extraction. PCR was used to amplify the COMT gene, followed by sequencing to identify variants. Standardized scales were used for gauging the severity of the symptoms. Results: Two novel changes in a single nucleotide (SNPs) (non-synonymous) were identified in the COMT gene in exon -4 of two female SCZ patients out of 80 patients are exon 4: c.449A>T [Gln150Leu] and c.114G>C [p. Ala123Pro]. The c.449A>T [Gln150Leu] variant was associated with paranoid-type positive symptoms, while c.114G>C [p. Ala123Pro] was associated with catatonic-type positive symptoms, while their challenging other symptoms like as pre-menopausal, obesity and endocrine symptoms would have an adverse effect on their lifestyle activity. Conclusion: In this study results identified novel COMT gene variants linked with specific symptomatology in SCZ patients’ variants that may contribute to the phenotypic abnormalities notified in SCZ. Further study with larger cohorts is needed to validate these findings and explore their influence on customized therapies.