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Thiopurine methyltransferase activity in a Spanish population sample: decrease of enzymatic activity in multiple sclerosis patients

Unidad de Toxicología Molecular Hepática, Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, E-28871 Alcalá de Henares, Spain

J Fueyo

Unidad de Toxicología Molecular Hepática, Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, E-28871 Alcalá de Henares, Spain

O Escribano

Unidad de Toxicología Molecular Hepática, Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, E-28871 Alcalá de Henares, Spain

M J Piña

Unidad de Toxicología Molecular Hepática, Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, E-28871 Alcalá de Henares, Spain

P Redondo

Unidad de Toxicología Molecular Hepática, Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, E-28871 Alcalá de Henares, Spain

C Cara

Scientific Department, Celltech Pharma, Spain

I D Román

Unidad de Toxicología Molecular Hepática, Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, E-28871 Alcalá de Henares, Spain

M D Fernández-Moreno

Unidad de Toxicología Molecular Hepática, Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, E-28871 Alcalá de Henares, Spain

L G Guijarro

Unidad de Toxicología Molecular Hepática, Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, E-28871 Alcalá de Henares, Spain, luis.gonzalez{at}uah.es

The present study was performed in order to obtain the thiopurine methyltransferase (TPMT) activity frequency distribution histogram in a Spanish population. A total of 3640 Spanish clinical laboratory samples were evaluated, which included 1249 patients with Crohn’s disease, 589 with ulcerative colitis, 348 with multiple sclerosis (MS), 487 with several autoimmune diseases different from the above-mentioned diseases and 967 a donor group. We have measured the TPMT activity in red blood cells (RBCs) by a radiochemical method, using S-adenosyl-L-[methyl-³H]methionine as methyl donor. The different groups present in their entirety a normal distribution histogram and a wide range of TPMT activity from 0 to 41 U/ml RBCs. The differences found between the Spanish population TPMT activity frequency distribution histogram and the pattern previously described in a North American population were not due to azathioprine treatment or gender. The effect of autoimmune diseases on TPMT activity was evaluated: the enzymatic activity was similar in the donor group (19.9-6.3 U/ml RBCs) and in the patients with Crohn’s disease (20.0-5.8 U/ml RBCs) and ulcerative colitis (19.7-6.1 U/ml RBCs); however, it decreased significantly (p<0.0001) in MS patients (17.1-6.1 U/ml RBCs) with respect to the donor group. In conclusion, our results show that the Spanish population TPMT distribution is closer to that of the Jewish population of Israel than to North American populations, and that in MS the enzymatic activity of TPMT decreases significantly. This observation may take into account the usage of azathioprine as therapeutic agent in Spanish MS patients.

Key Words: Crohn's disease • erythrocyte • multiple sclerosis • polymorphism • thiopurine methyltransferase • ulcerative colitis

Multiple Sclerosis, Vol. 8, No. 3, 243-248 (2002)
DOI: 10.1191/1352458502ms796oa


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