Determination of intra-ethnic differences in the polymorphisms of thiopurine S-methyltransferase in Chinese.
BACKGROUND
Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. Several mutations in the TPMT gene have been identified which correlate with a low activity phenotype. The molecular basis for TPMT deficiency is not well defined in minority Chinese. We investigated differences in the activity of TPMT and the frequencies of mutant TPMT alleles in 4 ethnic groups of Chinese.


METHODS
The frequency of 4 common TPMT mutant alleles, TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C, were determined in healthy subjects from Han (n=312), Jing (n=103), Yao (n=126) and Uygur Chinese (n=160) by allele-specific PCR and PCR-restriction RFLP analysis. TPMT activity in erythrocytes was determined by HPLC.


RESULTS
There was no significant difference in the mean TPMT activity between all ethnic groups studied and no subject with TPMT deficiency was found in all populations studied. TPMT*3C was found in 2.2% of Han and 1.9% of Jing Chinese. TPMT*2, TPMT*3B and TPMT*3A alleles were not detected in any of the Han or Jing Chinese tested. In contrast, 3.7% of Uygur Chinese had TPMT*3C and TPMT*3A alleles. Neither allele was detected in Yao Chinese. The overall frequencies of variant TPMT allele in Uygur were higher than in Han or Jing Chinese. However, neither the overall frequency of mutant TPMT alleles nor the genotype frequencies were significantly different between Han, Jing, Yao and Uygur Chinese.


CONCLUSIONS
The TPMT*3C was the most prevalent allele in Han, Jing and Uygur Chinese, while TPMT*3A is a rare allele in Uygur Chinese who belong to Caucasian. Ethnicity may be an important factor affecting the variability in response to thiopurine chemotherapy.
Zhang
Jian-Ping
JP
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China.
Zhou
Shu-Feng
SF
Chen
Xiao
X
Huang
Min
M
D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002681:China; D017931:DNA Primers; D005006:Ethnicity; D005260:Female; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D017931:DNA Primers; D008780:Methyltransferases; C022745:thiopurine methyltransferase