Assessment of N-Acetylation Genetic Polymorphism in Japanese Using Bhattacharya's Method.

概要

論文の詳細を見る
The genetically controlled isoniazid N-acetylation capacity was determined in 340 unrelated Japanese subjects residing in Japan. After an oral dose of 300 or 400mg of isoniazid, the "molar acetylation ratio" (INH/AcINH) in 8hr urine was measured by high-performance liquid chromatography. Bhattacharya's analysis was performed with the data obtained from INH/AcINH. The frequency distribution of the molar acetylation ratio showed an apparent trimodal pattern. Trimodal distributions were estimated to be 40 (rapid actylator: RA): 50 (intermediate: IM): 10 (slow acetylator: SA). These results suggested antimode of -0.85 and -0.325 (log INH/AcINH) discriminating trimodal distributions (RA>-0.85, -0.85<IM<-0.325, -0.325<SA). These 340 unrelated Japanese subjects were classified as RA (136 subjects), IM (170 subjects), or SA (34 subjects). This result was similar to previous studies. Although the present work was focused on isoniazid phenotyping, Bhattacharya's method may be applicable to other genetic polymorphic drugs such as dapsone, mephenytoin, and metoprolol.