Method of predicting a predisposition to QT prolongation
The present invention describes an association between genetic polymorphisms in the FAM13A1 (family with sequence similarity 13, member A1) gene and a predisposition to prolongation of the QT interval, and provides related methods for the prediction of such a predisposition, the administration of QT interval- prolonging compounds to individuals having such a predisposition, and determining whether a compound is capable of inducing QT prolongation.
1. A method of administering iloperidone or a metabolite thereof to a human individual, the method comprising:
determining the individual's FAM13A1 (family with sequence similarity 13, member A1) gene sequence at the rs3775378 locus; and
in the case that the individual's FAM13A1 gene sequence at the rs3775378 locus is TT, administering to the individual a first quantity of iloperidone or a metabolite thereof, and
in the case that the individual's FAM13A1 gene sequence at the rs3775378 locus is non-TT, administering to the individual a second quantity of iloperidone or a metabolite thereof, wherein the first quantity is less than the second quantity.
2. The method of claim 1 , further comprising: determining the individual's CYP2D6 genotype.
3. The method of claim 1 , wherein the method comprises administering iloperidone to the human individual.
4. The method of claim 1 , wherein the method comprises administering a metabolite of iloperidone to the human individual, wherein the metabolite is 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanol.
5. A method of administering a compound that is iloperidone or a metabolite thereof to an individual suffering from long QT syndrome (LQTS), the method comprising:
determining the individual's FAM13A1 (family with sequence similarity 13, member A1) gene sequence at the rs3775378 locus; and
administering to the individual either a first quantity or a second quantity of the compound based on the individual's FAM13A1 gene sequence at the rs3775378 locus,
wherein the second quantity is larger than the first quantity, and
wherein the first quantity is administered to the individual if the individual has a TT genotype at the rs3775378 locus, and wherein the second quantity is administered to the individual if the individual has a genotype at the rs3775378 locus that is not TT.
6. The method of claim 5 , further comprising: determining the individual's CYP2D6 genotype.
7. The method of claim 5 , wherein the compound is iloperidone.
8. The method of claim 5 , wherein the compound is a metabolite of iloperidone, and is 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanol.
9. The method of claim 3 , wherein the second quantity of iloperidone is 24 mg/day, and the first quantity of iloperidone is less than 24 mg/day.
10. The method of claim 7 , wherein the second quantity of iloperidone is 24 mg/day, and the first quantity of iloperidone is less than 24 mg/day.