NEW POLYMORPHISMS IN ABCB1 ASSOCIATED WITH A LACK OF CLINICAL RESPONSE TO MEDICAMENTS

摘要

The present invention relates to methods, compositions, kits and reagents for determining the prognosis of a clinical response in a human patient to a medicament which acts in the central nervous system (CNS) and which is a substrate of the ABCB1 protein. Further, the invention relates to a combination of medicaments for the treatment of human patients having specific polymorphisms in the ABCB1 gene.

主权项

1. A method for determining the prognosis of a clinical response to a central nervous system (CNS)-active medicament which is a substrate of the ABCB1 protein and treating a human patient suffering from depressive disorder dysthymia and/or bipolar disorder, comprising
(a) determining
(i) the presence of the minor C allele of polymorphism rs4148740 or the presence of a minor allele of a polymorphism which is in linkage disequilibrium with said polymorphism rs4148740 and(ii) the presence of the minor T allele of polymorphism rs2235015 or the presence of a minor allele of a polymorphism which is in linkage disequilibrium with said polymorphism rs2235015,using genotyping analysis in a human patient suffering from depressive disorder, dysthymia and/or bipolar disorder,
wherein said genotyping analysis allows
(i) a discrimination between polymorphism rs4148740 or a polymorphism which is in linkage disequilibrium with said polymorphism rs4148740 and other polymorphisms, which are not in linkage disequilibrium with said polymorphism rs4148740,(ii) a discrimination between polymorphism rs2235015 or a polymorphism which is in linkage disequilibrium with said polymorphism rs2235015 and other polymorphisms, which are not in linkage disequilibrium with said polymorphism rs2235015,(iii) a discrimination between the major T allele and the minor C allele of said polymorphism rs4148740 or the major allele and the minor allele a polymorphism which is in linkage disequilibrium with said polymorphism rs4148740, and(vi) a discrimination between the major C allele and the minor T allele of said polymorphism rs2235015 or the major allele and the minor allele a polymorphism which is in linkage disequilibrium with said polymorphism rs2235015; (b) selecting
(i) a patient where the minor C allele of said polymorphism rs4148740 or the minor allele of a polymorphism which is in linkage disequilibrium with said polymorphism rs4148740 is present, and/or(ii) a patient where the minor T allele of said polymorphism rs2235015 or the minor allele of a polymorphism which is in linkage disequilibrium with said polymorphism rs2235015 is present, wherein the presence of the minor allele of the polymorphism in the ABCB1 gene of said patient indicates an improved response to a central nervous system (CNS)-active medicament which is a substrate of the ABCB1 protein as compared to patients where the major allele is present; and (c) administering a medicament which is an ABCB1 substrate to said patient.