Genetic diagnosis for QT prolongation related adverse drug reactions

摘要

The specification is directed to a method of diagnosing whether a subject is predisposed to an adverse reaction to one or more pharmaceutical agents which may induce a prolonged QT interval or acquired LQTS in that individual. The diagnosis is genetic analysis of at least two polymorphisms or mutations which the individual may have, which are associated with an increased risk for prolonged QT intervals or Torsades de Pointes (TdP). Genetic screening for determining the predisposition of prolonged QT intervals induced by a pharmaceutical agent is performed by identifying genetic polymorphisms or mutations located in at least two classes of genes, wherein the genes are (1) LQT genes, (2) altered sensitivity genes (e.g., MiRP1) or (3) increased exposure genes (e.g., MDR genes or P450 cytochrome genes). The specification is also directed to compositions and kits for determining such predispositions to adverse drug reactions.