Testing for heterogeneity in genetic polymorphism of N-acetylation using isoniazid by metameters--probit, logit, and arcsine transformation

To investigate genetic polymorphism of N-acetylation in Japanese population we measured isoniazid (INH) and acetylisoniazid (AcINH) in the urine of 340 unrelated Japanese subjects. For the detection of polymorphism, we used probit analysis, logit analysis, and arcsine transformation of the logarithm of molar acetylation ratio (log (INH/AcINH)). The observed antimodes were -0.85 and -0.325 for the probit, 4.899 and 7.154 for the logit, 43.85 and 71.57 for the arcsine analysis plot. Probit and arcsine analysis were sensitive for the separation of intermediate from slow acetylators, while logit analysis was sensitive for the separation of rapid from intermediate acetylators. Clinically it is important to know to which genetic group the patient belongs because we may have to increase the dosage for the rapid acetylators to achieve the desired therapeutic effect, while we may have to reduce the dosage for slow acetylators in whom the incidence of side effect is high.