Methods and systems are provided herein that are based on the effects of genetic variations on the biological activities associated to rostafuroxin in an individual. In particular, compositions, methods and systems are herein described that are based on an indentified influence on an individual response to rostafuroxin of one or more polymorphisms in an intergenic or intragenic region of a gene selected from the group consisting of KCNS3, THSD7A, FAM46A, LOC389970, HLA-G, and TTC29, and/or a genetic variation in linkage disequilibrium therewith.