ACETYLATION POLYMORPHISM AND LEPROSY

The sulfones are the drug of choice in the treatment of leprosy, with dapsone as the clear favorite. The major route for dapsone metabolism leading to its inactivation and excretion is via acetylation by hepatic N-acetyl transferase (NAT), as is the case with isoniazid (INH) and sulfamethazine (SMZ). The enzyme is known to exhibit genetic polymorphism. The object of the present study is mainly to determine the incidence of acetylator phenotype in a population of leprosy patients with a view to evaluating the degree of association, if any, between phenotype and the disease. Obviously a knowledge of the incidence of the phenotypes may provide a valuable contribution to the institution of more rational and successful therapy. In the normal or control subjects, as well as in the leprosy patients, the frequency distribution histograms of the percentage acetylsulfamethazine in urine and serum samples are bimodal, and this indicates the existence of a genetic polymorphism. Based on the bimodality, individuals were classified as either "rapid" or "slow" acetylators, and the incidence of the slow acetylator phenotype of about 51% was observed in the leprosy population. This gives a relatively high incidence of the allele controlling the slow acetylator (q=0.73). Although there is evidence that the mean percentage of SMZ acetylated in leprosy patients of the slow acetylator phenotype is significantly higher than that observed for the same phenotype in the controls (t=4.86, P<0.02), statistical analyses show that there is no association between the slow acetylator phenotype and the disease. Most of the individuals in the slow acetylator phenotype tend to show some adverse reactions when a total weekly dose of 600 mg is given. Such adverse reactions include heightened lepra reactions, blurring of vision, and headache. These reactions, we think, are due to accumulation of the drug in the subjects. This therefore brings into sharp focus the desirability of knowing the acetylator phenotype of an individual before the initiation of dapsone therapy. © 1990 Plenum Publishing Corporation.