Computational prediction and analysis of very high risk single nucleotide polymorphisms in human cytochrome P450 oxidoreductase gene

Abstract

Cytochrome P450 oxidoreductase (POR) is a highly polymorphic gene which is involved in metabolism of drugs and steroids through transfer of electron from NADPH to all CYP enzymes. In this study, we attempt to identify the very high risk single nucleotide polymorphisms in POR gene that would affect phenotype of the enzyme. The genetic variants in POR gene were retrieved from databases and analyzed with appropriate online computation tools. Very high risk non-synonymous SNPs were identified with 12 different sequence and structure homology based tools and evolutionary conservation tool (Consurf). Further the phenotype effect of the variant was assessed with MutPred2 and LigPlot. The very high risk non-coding variants were predicted with HaploReg V4 and RegulomeDB tools. The very high risk SNPs that may affect miRNA target sites were screened using PolymiRTs v3.0, miRNA SNP v2.0 and MirSNP. Among 4,601 variants in POR gene, 58 missense variants, 8 non-coding variants and three SNPs in miRNA target sites were found to be very high risk. These very high risk variants may regulate the expression and activity of cytochrome P450 oxidoreductase enzyme leading to differential drug and steroid metabolism by CYP enzymes.