Insilico Identification of Association between Nicotine Dependence and Pathogenic Missense Mutations of Catechol-O-Methyltransferase Gene

Abstract

Introduction: Oral cancers are known to be strongly associated with the usage of tobacco, which is majorly composed of nicotine. Genetic studies evidenced the nicotine addiction as hereditary. AIM: The aim of the present study is to analyse any genetically functional missense mutations in Catechol-O-methyl-transferase (COMT) gene and derive an association with nicotine dependence that might influence tobacco habit initiation, addiction, and cessation. Methodology: The study involved an insilico analysis about the association between COMT gene and nicotine dependence. This was done with the help of different databases available in website. Initially, database called Ensembl (https://asia.ensembl.org) was used to pool the genetic data on missense mutations of the human COMT gene. The collected data was then fed into computational tools such as SIFT, PolyPhen, PROVEAN, I-Mutant, MutPred to discover the pathogenic mutations if exists. Results: Among 78 missense mutations collected, 74 were identified as damaging variants in which 8 variants were found to cause increased protein stability and 66 were found to cause decreased protein stability. Among those 66 missense variants causing decreased protein stability, 25 variants were identified as highly pathogenic while 19 variants were identified as pathogenic. Conclusion: The in-silico analysis discovered the existence of highly pathogenic mutations in COMT gene which might have a strong association with nicotine dependence that can influence the tobacco habit initiation, addiction, and cessation.