Pathogenic Missense Mutations in Nicotine-metabolizing Cytochrome P450 2A6 Gene – An In silico Study

Abstract

Introduction: Nicotine is an environmental agent that can have a significant impact on the emergence of nicotine dependence when it interacts with particular candidate nicotine genes. Pharmacogenetics may have a role in the interindividual difference in adolescent smoking cessation. Identification of missense mutations (which are deleterious) in advance will help to formulate medication targeting it, to prevent the consequences in the future. The current study aimed to identify more potential and functional mutations of the cytochrome P450 2A6 (CYP2A6) gene by employing computational tools. Materials and Methods: The Ensembl database was used to collect the data on missense mutations of the human CYP2A6 gene. Computational tools such as Sorting Intolerant From Tolerant, Polymorphism Phenotyping, and PROtein Variation Effect ANalyzer are used to identify and screen missense mutation. One hundred and thirty missense mutations were identified and screened. The stability of protein variants and their pathogenicity were identified using I-Mutant and MutPred, respectively. Results: One hundred and eighteen single-nucleotide polymorphisms were determined to be harmful among the 130 missense variants that were examined, as predicted by all three of the computational tools mentioned in the methodology section. I-Mutant Suite identified about 104 variants with decreased stability and the other 14 variants showed increased stability. MutPred tool identified that out of the 118 missense variants, 69 were found to be highly pathogenic, 33 were found to be pathogenic, and two of them were not pathogenic. Conclusions: Nearly a hundred alleles in the CYP2A6 gene were identified as potentially pathogenic variants using data mining.

Keywords

• cytochrome p450 2a6
• genetics
• in silico
• mutation
• tobacco