Figure 2

Examples of regulatory element variants affecting promoter activity and microRNA binding. (a) A promoter variant in the gene encoding vitamin K epoxide reductase complex subunit 1 (VKORC1): VKORC1 is an enzyme that converts vitamin K into an active form that is vital for blood coagulation and is a warfarin target. Individuals with the -1639A promoter variant have diminished levels of this enzyme, resulting in increased sensitivity to a typical warfarin dose. (b) Certain forms of cancer become resistant to the chemotherapeutic cisplatin. This is the result of the miR-200b/200c/429 family of microRNAs, which nullify the action of the drug by binding to and downregulating AP-2α mRNA, a key effector of cisplatin treatment. In cell lines harboring a TFAP2A 3' UTR polymorphism, rs1045385 A>C, miR-200b/200c/429 cannot bind its mRNA target, resulting in increased responsiveness to cisplatin.