Frecuencia y distribución de las variantes alélicas del gen de la tiopurina S-metiltransferasa en distintos grupos étnicos españoles

Abstract

Thiopurine S-methyltransferase (TPMT) metabolizes thiopurine drugs regulating their cytotoxicity and clinical response. TPMT activity is inherited as an autosomal recessive trait and several mutations in the TPMT gene have been identified which correlate with a low activity phenotype. A variable number of tandem repeat within the TPMT promoter has been reported to modulate the levels of this enzyme activity. The allelic variants of the TPMT gene were analyzed in ethnic groups living in Spain. The frequency of 4 allelic variants of the TPMT gene as well as the genotype in the promoter region were analyzed in 138 Spanish blood donors, 95 gypsies and 51 Basque subjects. In the group of 138 blood donors, we identified: 13 carriers of a mutated TPMT allele (*3A, *3B, *3C), one homozygous TPMT*3B and a compound heterozygote (TPMT*3A/TPMT*3B). In the Basque group, 3 subjects were TPMT*3A carriers and one case was a TPMT*3B heterozygote. In the gypsy group one subject carried a TPMT*3A allele and 3 were compound heterozygotes TPMT*3A/TPMT*3B. The TMPT*3A was the most frequent mutant alelle. As for the polymorphic tandem repeat in the 5' flanking region of the TPMT gene, alleles with 4 or 5 repeats made up the vast majority (96%) of the chromosomes in the control group of Spanish subjects. This figure decreased to 75% in Basques and to 62% in gypsies, in whom 37% of the alleles contained more than 5 tandem repeats. The frequencies of the mutant TPMT alleles observed in the 3 groups are similar to those reported in Caucasian populations.