Affect to drug metabolism CYP3A4 gene polymorphism, and its use

摘要

PROBLEM TO BE SOLVED: To identify new polymorphism lowering a drug metabolism activity of CYP3A4 and to provide a method for testing related to the drug metabolism activity using the polymorphism as an index.;SOLUTION: Three types of nonsynonymous single nucleotide polymorphism (T185S, L293P and T363M) of a CYP3A4 gene are discovered by using 34 kinds of established cell lines derived from Japanese. Furthermore, T185S mutant type CYP3A4 is found to lower an activity for hydroxylating testosterone as compared with that of wild type CYP3A4. Thereby, the drug metabolism activity can be tested by using the polymorphism of the CYP3A4 gene producing the T185S as an index. When the drug is not metabolized with the CYP3A4, adverse effects of the drug are considered to easily appear. The possibility for predicting the adverse effects of the drug is greatly expected by the test.;COPYRIGHT: (C)2004,JPO