Abstract
Isoniazid inactivation was studied in a sample of 100 subjects from Central Thailand. The frequency of the allele AcS (resulting in “slow” inactivation in the homozygous state) was calculated as 0.755. There is evidence for a simply additive dosage effect of the two genes AcR and AcS. The results are discussed with regard to other population studies and to recent findings concerning isoniazid inactivation and the activity of the involved enzymes in nonhuman primates.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Armstrong, A. R., and H. E. Peart: A comparison between the behavior of Eskimos and non-Eskimos to the administration of isoniazid. Amer. Rev. resp. Dis. 81, 588 (1960).
Devadatta, S., P. R. Gangadharam, R. H. Andrews, W. Fox, C. V. Ramakrishnan, J. B. Selkon, and S. Velu: Peripheral neuritis due to isonaizid. Bull. Wld Hlth Org. 23, 587 (1960).
Evans, D. A. P., V. A. McKusick, and K. A. Manley: Genetic control of isoniazid metabolism in man. Brit. Med. J. 1960/II, 485.
Gangadharam, P. R. J., and J. B. Selkon: The association between response to treatment with isoniazid and the rate of inactivation of isoniazid in South Indian patients with pulmonary tuberculosis. Proc. XVI. Internat. Tuberc. Conf. 2, 556 (1961).
Goedde, H. W., W. Schloot u. H.-G. Benkmann: Arbeitsvorschrift zur Bestimmung des Isonicotinsäurehydrazids (INH) im Serum. Chemotherapia (Basel) 12, 61 (1967a).
—: Enzymatische Umsetzung von Isonicotinsäurehydrazid. Angew. Chem. 77, 1020 (1965).
—: Enzymatische Umsetzung von Isonicotinsäurehydrazid — ein pharmacogenetisches Problem. Arzneimittel-Forsch. 16, 1030 (1966).
Goedde, H. W., W. Schloot u. A. Valesky: Individual different response to drugs: Characterisation of an INH-acetylating system in rhesus monkeys. Biochem. Pharmacol. 16 (1967b) (in press).
—: Pharmakogenetik (Klinische Probleme und biochemisch-genetische Grundlagen). Med. Klin. 59, 1849 (1964a).
—: Studies on pharmacogenetics — I. The enzymic acetylation of isonicotinic acid hydrazide (INH). Biochem. Pharmacol. 13, 1671 (1964b).
—: Pharmakogenetik: Untersuchungen zum Polymorphismus der Acetylierung von Isonicotinsäurehydrazid (INH). Humangenetik 1, 141 (1964c).
Harris, H. W.: High-dose isoniazid compared with standard-dose isoniazid, with PAS in the treatment of previously untreated cavitary pulmonary tuberculosis. Transact. Res. Conf. Pulmon. Dis. 20, 39 (1961).
Jenne, J. W.: Partial purification and properties of the isoniazid transacetylase in human liver. Its relationship to the acetylation of p-aminosalicylic acid. J. clin. Invest. 44, 1992 (1965).
Knight, R. A., M. J. Selin, and H. W. Harris: Genetic factors influencing isoniazid blood levels in humans. Transact. 18th Conf. Chemotherapy Tuberc., VA-Armed Forces, Washington, p. 52, 1959.
Maher, J. R., J. M. Whitney, J. S. Chambers, and D. J. Stanonis: The quantitative determination of isoniazid and p-aminosalicylic acid in body fluids. Amer. Rev. Tuberc. 76, 852 (1957).
Mitchell, R. S., D. K. Riemenschneider, J. R. Harsch, and J. C. Bell: New information on the clinical implications of individual variations in the metabolic handling of antituberculous drugs — particularly isoniazid. Transact. 17th Conf. Chemotherapy Tuberc.c VA-Armed Forces, Washington, pag. 77, 1958.
Nanakorn, S., V. Minnich, and A. I. Chernoff: Studies on hemoglobin E: II. The incidence of hemoglobin E in Thailand. J. Lab. clin. Med. 47, 490 (1956).
Peters, J. H., K. S. Miller, and P. Brown: The determination of isoniazid and its metabolites in human urine. Ann. Biochem. 12, 379 (1965).
Schloot, W., and H. W. Goedde: Studies on the polymorphism of isoniazid (INH) acetylation in rhesus monkeys (Macaca mulatta). Acta genet. (Basel) (in press).
Schmiedel, A.: The problem of rapid isoniazid inactivation. Proc. XVIth Internat. Tuberc. Conf. 2, 508 (1961).
Spencer, N., D. A. Hopkinson, and H. Harris: Quantitative differences and gene dosage in the human red cell acid phosphatase polymorphism. Nature (Lond.) 201, 299 (1964).
Sunahara, S.: Isoniazid metabolism. Clinical, genetical and geographical study. Kekkaku 36, 521 (1961a).
—: Les problèmes du métabolisme de l'isoniazide. Med. Thorac. 20, 289 (1963a).
Sunahara, S. et M. Urano and K. Kawai: Biochemical and genetical studies on isoniazid metabolism. Ann. Rep. 3, Tokyo Nat. Chest Hosp. (1963b).
—: Further observations on trimodality of frequency distribution curve of biologically active isoniazid blood levels and “cline” in frequencies of alleles controlling isoniazid inactivation. Acta tuberc. pneum. scand. 43, 181 (1963c).
—: Genetical and geographic studies on isoniazid inactivation. Science 134, 1530 (1961b).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schloot, W., Blume, K.G., Goedde, H.W. et al. Studies on isoniazid conversion in Thailand. Hum Genet 4, 274–279 (1967). https://doi.org/10.1007/BF00292200
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00292200