[Frequency of thiopurine S-methyltransferase alleles in different ethnic groups living in Spain].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
The frequencies of the mutant TPMT alleles observed in the 3 groups are similar to those reported in Caucasian populations.
Corominas
Hector
H
Departament de Medicina Interna, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. hcorominas@hsp.santpau.es
Domènech
Montserrat
M
del Río
Elisabeth
E
Gich
Ignasi
I
Domingo
Pere
P
Baiget
Montserrat
M
D000483:Alleles; D006801:Humans; D008780:Methyltransferases / Q000235:genetics*; D044469:Racial Groups; D013030:Spain
D008780:Methyltransferases; C022745:thiopurine methyltransferase