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 less than 0.02), statistical analyses show that there is no association between the slow acetylator phenotype and the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Eze
L C
LC
Department of Biochemistry, University of Nigeria, Nsukka.
Okpogba
A N
AN
Ogan
A U
AU
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007918:Leprosy / Q000235:genetics*; D009549:Nigeria; D010641:Phenotype; D011110:Polymorphism, Genetic; D013418:Sulfamethazine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use / Q000652:urine
D013418:Sulfamethazine; D000123:Acetyltransferases