Tube&e (1975), 56, 199
OF THE ACETYLATOR PHENOTYPE NIGERIAN POPULATION
IN A NORTHERN
1. W. FAWCETT” Department
Ahmadu Bell0 University
PATRICIAT. GAMMON M.R.C.
Unit .for Laboratory
Royal Postgraduate W12 OHS
The sulphadimidine method was used to determine the acetylator phenotype in tuberculosis patients and hospital workers at Ahmadu Bello University Hospital, Zaria, Nigeria. The method gave good discrimination between slow and rapid acetylators. The proportion of slow acetylators in the whole group was 49 per cent and this is similar to other results from Negro populations.
La mCthode B la sulfadimidine a t3t utilisee pour dCterminer le phtnotype acCtylateur chez des malades tuberculeux et des employ& hospitaliers B l’hopital de l’universitt Ahmadu Bello, & Zaria, Nigeria. Cette mtthode a fait une bonne discrimination entre acCtyleurs lents et rapides. La proportion d’adtyleurs lents du groupe entier, a &5 de 49 pour cent et cette proportion est semblable g celle d’autres Ctudes faites sur des populations noires.
ZUSAMMENFASSUNG Mittels der Sulfadimidin-Methode wurde der Phlnotyp der Azetylierung bei Tuberkulosekranken und Angestellten der UniversitPtsklinik Ahmadu Belle, Zaria (Nigeria) bestimmt. Die Methode erlaubt eine klare Trennung zwischen langsamer und schneller Azetylierung. Der Anteil der Personen mit langsamer Azetyliernng betrlgt 49 Prozent, was gut mit den Resultaten iibereinstimmt, die an anderen afrikanischen Gruppen gewonnen wurden.
*Reprint requests should be addressed to Dr. 1. W. Fawcett, at the Cardiothoracic Fulham Road, London, SW3 6HP.
Se empled el mttodo de la sulfadimidina para determinar el fenotipo acetilador en pacientes tuberculosos v en obreros hosnitalarios en el HosDital Ahmadu Bello. en Zaria, Nigeria. El mitodo apro& una buena discrimacibn entre Bcetiladores lentos’ y rhpidos. En el conjunto de1 grupo la proporci6n de acetiladores lentos fue del 49 por centaje. similar a otros resultados en poblaciones negras. _._.
Isoniazid is inactivated in man by acetylation in the liver and a population may be divided into slow and rapid inactivators (Evans and White, 1964; Evans, Manley and McKusick, 1960). Isoniazid and sulphadimidine are acetylated by a similar enzymatic process (White and Evans, 1967) and under the same genetic control (Evans, Manley and McKusick, 1960; Evans and White, 1960). The use of the sulphadimidine acetylation test to determine the acetylator phenotype in population surveys has the advantages of ease of administration, relatively simple estimation and stability of sulphadimidine and its metabolites in stored serum (Evans, 1969; Rao and others, 1970; ViznerovB. Slavikovri and Ellard, 1973). It is, therefore, particularly suitable for use in the tropics and this paper describes the results obtained in an indigenous African population in Zaria. Nigeria, the first published results for West Africa. Methods
Samples of serum (6 hours) were obtained from 109 indigenous African subjects after dosage with 40 mg/kg 0e7sulphadimidine, according to the dosage schedule described by Evans (1969). Eighty of the subjects were in-patients at the Tuberculosis Annexe of Ahmadu Bello University Hospital, Zaria and the remaining 29 were healthy volunteers from the hospital staff. Antituberculosis drugs were withheld from the patients for 2 days before the test and to check that this had been done, a urine sample was tested for acetylisoniazid by the method of Eidus and Hamilton (1964) before administration of sulphadimidine. Serum samples were stored at -20°C until analysis in London when the concentrations of free sulphadimidine and acid hydrolysable (free plus acetylated) sulphadimidine were determined by the Bratton-Marshall procedure (Varley. 1962). Results
The results obtained for the 109 subjects are illustrated in the figure. Ninety-three of the subjects were from the Hausa tribe, the majority ethnic group in northern Nigeria. The remaining 16 people were from 9 other distinct tribal groups in Nigeria. Previous work has shown (ViznerovB, Slavikova and Ellard, 1973) that the level of 45 per cent sulphadimidine acetylated in the plasma at 6 hours provides the most efficient discriminator between slow and rapid acetylators. On this basis 53 (49 per cent) of the 109 subjects were slow inactivators and 56 (51 per cent) rapid inactivators. Of the Hausa subjects alone 43 (46 per cent) of the 93 were slow acetylators. Discussion
The proportion of slow acetylators in this population is similar to that (52-65 per cent) in other populations of Negro descent (Evans, Manley and McKusick, 1960; Mitchell, Bell and Riemensnider. 1960; Evans, 1962; Dufour, Knight and Harris, 1964: Ellard. Gammon and Tiitinen, 1975).
40 30 of Acetplated
50 60 Sulphadimidine
70 in Serum
FIG. 1 Distribution of 109 subjects according to the percentage of sulphadimidine acetylated in the serum at 6 hours.
The sulphadimidine method gave a clear-cut classification of the study population into slow or rapid acetylators. Subjects may be classified according to the percentage acetylated sulphadimidine in either blood or urine after the test dose and it has been suggested by Rao and others (1970) that the urine test may be slightly more accurate than the blood test in classifying individual subjects. In European populations the urine test is also said to be easier to perform because of the greater ease with which specimens may be obtained. However, in a tropical environment it proved to be easier to take a single blood sample than to supervise the collection of a measured urine sample at a fixed time from an unsophisticated population. This more than compensated for the need to separate the serum from the sample after collection. We should like to thank Dr. G. A. Ellard for his help with this investigation and report. REFERENCES DLJFOUR, A. P., KNIGHT,R. A., & HARRIS,H. W. (1964). Genetics of isoniazid metabolism in Caucasian, Negro and Japanese populations. Science, 145, 391. EIDUS,L. & HAMILTON, E. J. (1964). A new method for the determination of N-acetylisoniazid in urine of ambulatory patients. American Review of Respiratory Disease, 89, 587. ELLARD,G. A., GAMMON, P. T. & TMNEN, H. (1975). Determination of the acetyiator phenotype using matrix isoniazid. Tuber&, 56. 203. EVANS,D. A. P., MANLEY,K. A. & MCKUSICK,V. A. (1960) Genetic control of isoniazid metabolism in man. &it&h Medical Journal, 2, 485. EVANS,D. A. P. (1962). Pharmocogenttique. Mddicine et Hygi&te (Get&e), 20, 905. EVANS,D. A. P. (1969). An improved and simplified method of detecting the acetylator phenotype. Journal ofMedical Genetics, 6, 405. EVANS, D. A. P. & WHITE,T. A. (1964). Human acetylation polymorphism. Journal of Laboratory and Clinical Medicine, 63, 394. MITCHELL, R. S., BELL,J. C. & RIEMENSNIDER, D. K. (1960). Further observations with isoniazid inactivation teats. Transactions of the 19th Conference on the Chemotherapy of Tuberculosis, P. 62, (Veterans Administration). RAO, K. V. N., MITCHISON, D. A., NAIR, N. G. K., PRBU, K. & TRIPATHY, S. P. (1970). Sulphadimidine acetylation test for classification of patients as slow or rapid inactivators of isoniazid. British Medical Journal, 3,495. VARLEY,H. (1962). Practical Clinical Biochemistry. 3rd edition, p. 634, Heinemann, London. VIZNEROV& A., SLAVIKOVA, Z. & ELLARD,G. A. (1973). The determination of the acetylator phenotype of tuberculosis patients in Czechoslovakia using sulphadimidine. Tubercle, 54, 67.