Skip to main content
NCBI home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1985 Oct;22(5):361–366. doi: 10.1136/jmg.22.5.361

The genetic control of phenformin 4-hydroxylation.

R R Shah, D A Evans, N S Oates, J R Idle, R L Smith
PMCID: PMC1049479  PMID: 4078865

Abstract

Previously published results of phenformin 4-hydroxylation in 195 unrelated white British volunteers and 87 family members of 27 randomly selected probands have been subjected to genetic analysis. The results clearly show that about 9% of this population has a genetically determined defect in carrying out this oxidation reaction. The character for the defect is inherited in a Mendelian autosomal recessive fashion. The polymorphism shows a substantial degree of dominance.

Full text

PDF
361

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beckmann R. The fate of biguanides in man. Ann N Y Acad Sci. 1968 Mar 26;148(3):820–832. doi: 10.1111/j.1749-6632.1968.tb27755.x. [DOI] [PubMed] [Google Scholar]
  2. Cooper R. G., Evans D. A., Whibley E. J. Polymorphic hydroxylation of perhexiline maleate in man. J Med Genet. 1984 Feb;21(1):27–33. doi: 10.1136/jmg.21.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dayer P., Balant L., Courvoisier F., Kupfer A., Kubli A., Gorgia A., Fabre J. The genetic control of bufuralol metabolism in man. Eur J Drug Metab Pharmacokinet. 1982 Jan-Mar;7(1):73–77. doi: 10.1007/BF03189547. [DOI] [PubMed] [Google Scholar]
  4. Devonshire H. W., Kong I., Cooper M., Sloan T. P., Idle J. R., Smith R. L. The contribution of genetically determined oxidation status to inter-individual variation in phenacetin disposition. Br J Clin Pharmacol. 1983 Aug;16(2):157–166. doi: 10.1111/j.1365-2125.1983.tb04980.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Evans D. A., Mahgoub A., Sloan T. P., Idle J. R., Smith R. L. A family and population study of the genetic polymorphism of debrisoquine oxidation in a white British population. J Med Genet. 1980 Apr;17(2):102–105. doi: 10.1136/jmg.17.2.102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Idle J. R., Mahgoub A., Sloan T. P., Smith R. L., Mbanefo C. O., Bababunmi E. A. Some observations on the oxidation phenotype status of Nigerian patients presenting with cancer. Cancer Lett. 1981 Feb;11(4):331–338. doi: 10.1016/0304-3835(81)90099-9. [DOI] [PubMed] [Google Scholar]
  7. Iselius L., Evans D. A. Formal genetics of isoniazid metabolism in man. Clin Pharmacokinet. 1983 Nov-Dec;8(6):541–544. doi: 10.2165/00003088-198308060-00005. [DOI] [PubMed] [Google Scholar]
  8. Lennard M. S., Silas J. H., Freestone S., Ramsay L. E., Tucker G. T., Woods H. F. Oxidation phenotype--a major determinant of metoprolol metabolism and response. N Engl J Med. 1982 Dec 16;307(25):1558–1560. doi: 10.1056/NEJM198212163072505. [DOI] [PubMed] [Google Scholar]
  9. Luft D., Schmülling R. M., Eggstein M. Lactic acidosis in biguanide-treated diabetics: a review of 330 cases. Diabetologia. 1978 Feb;14(2):75–87. doi: 10.1007/BF01263444. [DOI] [PubMed] [Google Scholar]
  10. Mahgoub A., Idle J. R., Dring L. G., Lancaster R., Smith R. L. Polymorphic hydroxylation of Debrisoquine in man. Lancet. 1977 Sep 17;2(8038):584–586. doi: 10.1016/s0140-6736(77)91430-1. [DOI] [PubMed] [Google Scholar]
  11. Mellström B., Bertilsson L., Säwe J., Schulz H. U., Sjöqvist F. E- and Z-10-hydroxylation of nortriptyline: relationship to polymorphic debrisoquine hydroxylation. Clin Pharmacol Ther. 1981 Aug;30(2):189–193. doi: 10.1038/clpt.1981.147. [DOI] [PubMed] [Google Scholar]
  12. Nattrass M., Sizer K., Alberti K. G. Correlation of plasma phenformin concentration with metabolic effects in normal subjects. Clin Sci (Lond) 1980 Feb;58(2):153–155. doi: 10.1042/cs0580153. [DOI] [PubMed] [Google Scholar]
  13. Oates N. S., Shah R. R., Idle J. R., Smith R. L. Genetic polymorphism of phenformin 4-hydroxylation. Clin Pharmacol Ther. 1982 Jul;32(1):81–89. doi: 10.1038/clpt.1982.130. [DOI] [PubMed] [Google Scholar]
  14. Oates N. S., Shah R. R., Idle J. R., Smith R. L. Influence of oxidation polymorphism on phenformin kinetics and dynamics. Clin Pharmacol Ther. 1983 Dec;34(6):827–834. doi: 10.1038/clpt.1983.257. [DOI] [PubMed] [Google Scholar]
  15. Oates N. S., Shah R. R., Idle J. R., Smith R. L. On the urinary disposition of phenformin and 4-hydroxy-phenformin and their rapid simultaneous measurement. J Pharm Pharmacol. 1980 Oct;32(10):731–732. doi: 10.1111/j.2042-7158.1980.tb13056.x. [DOI] [PubMed] [Google Scholar]
  16. Oates N. S., Shah R. R., Idle J. R., Smith R. L. Phenformin-induced lacticacidosis associated with impaired debrisoquine hydroxylation. Lancet. 1981 Apr 11;1(8224):837–838. doi: 10.1016/s0140-6736(81)92711-2. [DOI] [PubMed] [Google Scholar]
  17. Wiholm B. E., Alvan G., Bertilsson L., Sawe J., Sjöqvist F. Hydroxylation of debrisoquine in patients with lacticacidosis after phenformin. Lancet. 1981 May 16;1(8229):1098–1099. doi: 10.1016/s0140-6736(81)92260-1. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES