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Related Experiment Videos

Interethnic difference in thiopurine methyltransferase activity.

B Klemetsdal1, E Tollefsen, T Loennechen

  • 1Department of Pharmacology, University of Tromsø, Norway.

Clinical Pharmacology and Therapeutics
|January 1, 1992
PubMed
Summary

Saami populations exhibit significantly higher red blood cell thiopurine methyltransferase (TPMT) activity than Caucasians, suggesting potential differences in thiopurine drug metabolism and dosage requirements between ethnic groups.

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Area of Science:

  • Pharmacogenetics
  • Biochemistry
  • Population Genetics

Background:

  • Metabolic pathways often display genetic polymorphism and interethnic variations.
  • Red blood cell thiopurine methyltransferase (TPMT) activity, crucial for 6-mercaptopurine catabolism, is known to be polymorphic in Caucasians.
  • Interethnic variations in TPMT activity have not been extensively studied.

Purpose of the Study:

  • To investigate interethnic differences in red blood cell thiopurine methyltransferase (TPMT) activity.
  • To compare TPMT activity between Saami (Lappish) and Caucasian populations.

Main Methods:

  • Enzyme activity assays were performed on red blood cell samples.
  • TPMT activity was measured in 36 Saami and 50 Caucasian individuals.
  • Statistical analyses, including probit plots and frequency distribution histograms, were used to assess activity and identify polymorphism.

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Main Results:

  • Saami individuals showed significantly higher mean TPMT activity (17.0 +/- 3.3 U/ml RBC) compared to Caucasians (13.1 +/- 2.9 U/ml RBC) (p < 0.001).
  • Frequency distribution analysis indicated genetic polymorphism consistent with bimodal activity in both populations.
  • No significant differences in chronic diseases, drug consumption, age, or gender explained the observed interethnic variation.

Conclusions:

  • Significant interethnic variation exists in red blood cell TPMT activity, with higher levels observed in the Saami population.
  • These findings suggest that Saami individuals may metabolize thiopurine drugs differently than Caucasians.
  • Higher TPMT activity in Saami populations could necessitate adjusted dosages of thiopurine medications to ensure therapeutic efficacy and safety.