Molecular analysis of the thiopurine S-methyltransferase alleles in Bolivians and Tibetans.

BACKGROUND

Thiopurine drugs are used as immunosuppressant or cytotoxic drugs. Thiopurine S-methyltransferase (TPMT) methylates and thereby modulates the therapeutic and toxic effects of these drugs. The activity of TPMT is affected by genetic polymorphism of TPMT alleles, and these alleles have not been studied in Tibetans and Bolivians.

OBJECTIVES

To analyse the TPMT allelic frequencies in Tibetans and Bolivians.

METHODS

We developed an inexpensive method for collecting blood and extracting genomic DNA. Genomic DNA was extracted from blood spots of 50 Tibetans and 115 Bolivians. The frequencies of allelic variants of TPMT gene (TPMT1 to TPMT8) were determined using polymerase chain reaction-restriction fragment length polymorphism technique.

RESULTS

The allelic frequencies of TPMT1 were 99 and 93.48% for Tibetans and Bolivians, respectively. The corresponding allelic frequencies of TPMT3A were 0 and 6.52% and those of TPMT3C were 1.0 and 0%. No TPMT2, 3B, 3D, 4-8 were found in these two populations.

CONCLUSIONS

As with Caucasian populations, TPMT*3A is the most prevalent mutant allele in Bolivians. Our results may be of value in helping to guide the prescription of thiopurine drugs in these populations.