Thiopurine S-methyltransferase Gene (TMPT) Polymorphisms in a Mexican Population of Healthy Individuals and Leukemic Patients

Overview

Journal Med Oncol

Publisher Springer

Specialty Oncology

Date 2008 Jan 12

PMID 18188716

Citations 6

Authors

Lucia Taja-Chayeb

Silvia Vidal-Millan

Olga Gutierrez

Patricia Ostrosky-Wegman

Alfonso Duenas-Gonzalez

Myrna Candelaria

Affiliations

Soon will be listed here.

Abstract

Polymorphisms at the thiopurine S-methyltransferase coding gene (TPMT) determine enzyme activity and consequently, the development of toxicity secondary to thiopurines. Methods A total of 108 DNA samples from volunteer donors and 39 from patients with acute lymphoblastic leukemia (ALL) were analyzed. Genomic DNA from peripheral blood leukocytes was isolated by standard methods. TPMT gene fragments were amplified by PCR for exons 5, 7, and 10. Thereafter, these were analyzed by DHPLC for the most frequent mutant TPMT alleles. Results No elution profiles on DHPLC analysis, different from those previously reported, were documented. Frequency of functional allele polymorphisms was 17.6%, being the most frequent *3A (n = 13; 4.4%), followed by *3B (n = 5; 1.7%), *3C (n = 5; 1.7%), and *2 (n = 3; 1.0%). From 39 ALL patients, 22 were treated with thiopurines, and five from 10 with a functional polymorphism developed hematological toxicity (4 mild, 1 severe in a patient referred to our Hospital after developing pancytopenia while on treatment with thiopurine). Conclusions This is the first analysis of the polymorphisms at this gene in Mexican population. Since a direct relation has been documented within functional polymorphisms and enzyme activity, and DHPLC is a highly sensitive, rapid and efficient method, feasible to realize in any phase during the treatment of ALL patients, the routine typing of TPMT polymorphisms in the patients with ALL has been set in our Institution.

Citing Articles

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High frequency of mutant thiopurine S-methyltransferase genotypes in Mexican patients with systemic lupus erythematosus and rheumatoid arthritis.

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Polymorphisms of the thiopurine S-methyltransferase gene among the Libyan population.

Zeglam H, Benhamer A, Aboud A, Rtemi H, Mattardi M, Saleh S Libyan J Med. 2015; 10(1):27053.

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Imputation of TPMT defective alleles for the identification of patients with high-risk phenotypes.

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