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Aims: Ethnicity is an important variable influencing drug response. Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurine drugs. Previous population studies have identified ethnic variations in both phenotype and genotype of TPMT, but limited information is available within Chinese population that comprises at least 56 ethnic groups. The current study was conducted to compare both phenotype and genotype of TPMT in healthy Han and Yao Chinese children., Methods: TPMT activity was measured in healthy Chinese children by a HPLC assay (n = 213, 87 Han Chinese and 126 Yao Chinese). Allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) were used to determine the frequency of TPMT mutant alleles (TPMT*2, TPMT*3 A, TPMT*3B and TPMT*3C) in these children., Results: There was no significant difference in the mean TPMT activity between Han and Yao Chinese children. A unimodal distribution of TPMT activity in Chinese children was found and the mean TPMT activity was 13.32 +/- 3.49 U ml(-1) RBC. TPMT activity was not found to differ with gender, but tended to increase with age in Yao Chinese children. TPMT*2, TPMT*3B and TPMT*3A were not detected, and only one TPMT*3C heterozygote (Han child) was identified in 213 Chinese children. Erythrocyte TPMT activity of this TPMT*3C heterozygote was 12.36 U ml(-1) RBC. The frequency of the known mutant TPMT alleles was 0.2%[1/426] in Chinese children., Conclusion: The frequency distribution of RBC TPMT activity was unimodal. The frequency of the known mutant TPMT alleles in Chinese Children is low and TPMT*3C appears to be the most prevalent among the tested mutant TPMT alleles in this population.

Objective: This study was to investigate the gene mutation of thiopurine S-methyltransferase (TPMT) in Uygur Chinese., Methods: Polymerase chain reaction-based methods were used to analyze three commonly reported inactivating mutations-G238C, G460A and A719G., Results: One TPMT*3A heterozygote and five TPMT*3C heterozygotes were found in 160 Uygur Chinese subjects, and allele frequencies of TPMT*3A and TPMT*3C were 0.3% and 1.6%, respectively., Conclusion: TPMT*3C is a common mutant allele in Uygur Chinese, while TPMT*3A is a rare mutant allele in Uygur Chinese.

Objective: To investigate the mutant alleles of thiopurine S-methyltransferase (TPMT) among Jing Chinese., Methods: Polymerse chain reaction-single strand conformation polymorphism (PCR-SSCP) techniques were developed for assaying exons 5, 7 and 10 of the TPMT gene respectively and were used to detect mutant TPMT alleles among Jing Chinese., Results: Two cases of TPMT*3C (A719G) heterozygotes were identified in 103 Jing Chinese; other deleterious alleles such as TPMT*2 (G238C), TPMT*3A (G460A/A719G) and TPMT*3B (G460A) were not found; 27 cases of silent mutant allele TPMT*1S (T474C) were also identified (5 homozygotes and 22 heterozygotes)., Conclusion: The PCR-SSCP assay established and adopted in this study was sensitive and reliable, which could be used to detect mutant TPMT alleles. Allele frequency of TPMT*3C is low among Jing Chinese (1.0%), and TPMT*3C appears to be the most prevalent deleterious allele in this population.

Background & Objective: Several mutations in the thiopurine S-methyltransferase(TPMT) gene have been identified to correlate with a low activity or deficiency phenotype. The distribution of TPMT activity in Chinese and Caucasian populations is different, and the molecular basis has not yet to be determined. This study was designed to investigate the type and frequency of four kinds of mutant TPMT alleles of healthy Han Chinese., Methods: TPMT genotypes were determined in 225 healthy Han Chinese. Allele-specific PCR (ASPCR) and PCR-restriction fragment length polymorphism (RFLP) were used for analysis of G238C (TPMT*2), G460A and A719G (TPMT*3A,*3B,*3C)., Results: TPMT*2, TPMT*3B, and TPMT*3A were not detected in 225 healthy Han Chinese, and only six TPMT*3C heterozygotes were identified. The average TPMT activity of those TPMT*3C heterozygotes was (9.62+/-3.58) U/ml RBC. The frequency of TPMT mutant alleles was 1.33%(6/450) in healthy Han Chinese., Conclusion: The frequency of the known mutant TPMT alleles in Han Chinese population is low, and TPMT*3C appears to be the most prevalent among the known mutant TPMT allele in this population.

Replacing coenzyme F430, an Ni(I) F430-like cofactor derived from vitamin B12 (F430-B12) is revealed by DFT calculations to be able to catalyze methane formation in methyl-coenzyme M reductase with a barrier of 13.3 kcal mol−1, demonstrating the correctness of the route starting from vitamin B12. The structure–activity relationships of F430 and F430-B12 (especially the roles of the F ring) are discovered and several sources of inspiration promoting the application of F430-B12 are also obtained, coming closer to using F430 chemistry in man-made catalysis. [ABSTRACT FROM AUTHOR]