Genetic variation in the 3′-UTR of CYP1A2, CYP2B6, CYP2D6, CYP3A4, NR1I2, and UGT2B7: potential effects on regulation by microRNA and pharmacogenomics relevance

摘要: Introduction: Pharmacogenomics research has concentrated on variation in genes coding for drug metabolising enzymes, transporters and nuclear receptors. However, affecting microRNA could also play a role response. This project set out to investigate potential target sites 11 the extent of 3'-UTR six selected genes; CYP1A2, CYP2B6, CYP2D6, CYP3A4, NR1I2 UGT2B7. Methods: Fifteen prediction algorithms were used identify microRNAs predicted regulate genes. The 6 which topped list targets was sequenced 30 black South Africans. In addition, genetic variants within these investigated interference with mRNA-microRNA interactions. Potential effects observed determined using silico tools. Results: DMEs, receptors be (PXR), CYP3A4 interacting most microRNAs. majority identified interfere regulation. For example, variant, rs1054190C result presence binding site miR-1250-5p, while variant rs1054191G absence recognition miR-371b-3p, miR-4258 miR-4707-3p. seventeen, novel occurred sequences. Conclusion: harbours that is likely influence regulation specific by microRNA. followed functional validation aid decoding contribution 3'-UTR, some unexplained heritability affects Understanding each may lead identification markers targeted therapy therefore improve personalized treatment.