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.


OBJECTIVE
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 (TPMT*1 to TPMT*8) were determined using polymerase chain reaction-restriction fragment length polymorphism technique.


RESULTS
The allelic frequencies of TPMT*1 were 99 and 93.48% for Tibetans and Bolivians, respectively. The corresponding allelic frequencies of TPMT*3A were 0 and 6.52% and those of TPMT*3C were 1.0 and 0%. No TPMT*2, 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.
Lu
H-F
HF
Department of Molecular Medicine, China Medical University Hospital, Taichung, China.
Shih
M-C
MC
Hsueh
S-C
SC
Chen
C-M
CM
Chang
J-Y
JY
Chang
J-G
JG
D000483:Alleles; D001838:Bolivia / Q000453:epidemiology; D004247:DNA / Q000235:genetics; D005787:Gene Frequency; D006801:Humans; D008780:Methyltransferases / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018609:Tibet / Q000453:epidemiology
D004247:DNA; D008780:Methyltransferases; C022745:thiopurine methyltransferase