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.