Computational analysis of single nucleotide polymorphisms (SNPs) in human MPO gene

Backgrounds: Myeloperoxidase (MPO) as a haem peroxidase-cyclooxygenase enzyme with vital antimicrobialand antiviral role expressed circulating neutrophils, monocytes and some tissue macrophages.MPO is encoded by the MPO gene on chromosome ۱۷q۲۳. MPO-derived oxidants lead toinflammatory diseases, cancers, neurodegenerative diseases, cardiovascular diseases, kidneydiseases, and immune-mediated diseases. The aim of this study is the computational analysis ofsingle nucleotide polymorphisms (SNPs) in human MPO gene. Protein function and structurecan be altered by SNPs.Materials and Methods: Four in silico SNP prediction algorithms including PolyPhen,nsSNPAnalyzer, SNPs&GO and PROVEAN were used to identify functional SNPs in the codingregions of MPO gene and predict the effect of these variants on MPO function. Polymorphismsdata were retrieved from NCBI database of SNPs (dbSNP) for MPO gene.Results: In total, ۲۳۵ SNP for human MPO gene were showed by the dbSNP-NCBI databasewhich contained ۲۶ missense SNPs. The missense SNPs were used for our further investigations.۱۴ missense SNPs (۵۳%) are predicted to be probably damaging to MPO function, ۸ SNPs (۳۰%)are possibly damaging and ۴ missense SNPs (۱۵%) are benign by PolyPhen-۲ (Polymorphismphenotyping) algorithms predicting the potential impact of amino acid substitutions on proteinfunction and structure. Other three in silico tools predicted the same phenotypic effects of SNPswith their specific scores.Conclusion: These computational SNPs analysis can be beneficial for better understanding ofthe genetic causes of MPO mediated diseases like inflammatory diseases and cancers fordiagnosis and drug design.

کلیدواژه ها:

Myeloperoxidase ، Single nucleotide polymorphisms ، Inflammatory diseases ، in silico