Thiopurine methyltransferase activity in a Korean population sample of children*

Park-Hah, Jeong Ok; Klemetsdal, B.; Lysaa, Roy; Choi, Kyoung Ho; Aarbakke, Jarle

doi:10.1016/s0009-9236(96)90169-1

Cited by 40 publications

(24 citation statements)

References 33 publications

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“…Nevertheless, the graphical representation of TPMT data clearly showed that distribution differed depending on disease. It has been suggested that the unimodal or normal distribution of TPMT activity is more characteristic of some Jewish [17], French [18], or East Asian populations [19]. On the contrary, in other European [20] and North American [21] populations a more evident trimodal distribution has been described.…”

Section: Discussionmentioning

confidence: 99%

Thiopurine Methyltransferase Activity in Spain: A Study of 14,545 Patients

et al. 2007

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We sought to assess the activity of thiopurine methyltransferase (TPMT) in 14,545 Spanish patients with different diseases amenable to treatment with azathioprine/6-mercaptopurine (6-MP), and to evaluate the proportion of patients with low TPMT activity and therefore a higher risk of myelotoxicity with these drugs. TPMT activity in red blood cells (RBCs) was measured by a radiochemical method. The association between several clinical variables and TPMT activity was assessed by multiple linear regression. We included 14,545 patients: autoimmune hepatitis (n=359 patients), inflammatory bowel disease (n=7,046), multiple sclerosis (n = 814), myasthenia gravis (n=344), pemphigus (n=133), and other diseases (n=5,849). Mean TPMT activity was 20.1 +/- 6 U/mL, but differed depending on the disease (P<.001). TPMT distribution was low (<5) in 0.5%; intermediate (5.0-13.7) in 11.9%; or high (>or=13.8) in 87.6%. Only when TPMT activity was considered separately in each disease did it reveal a normal distribution. In the multivariate analysis, gender, hematocrit, and treatment with 5-aminosalicylates/steroids/azathioprine/6-MP statistically influenced TPMT activity, although, probably, in a clinically irrelevant manner. This study shows, in a large sample of 14,545 patients, that 0.5% had low TPMT activity, indicating a higher risk of myelotoxicity with azathioprine/6-MP, a figure similar or slightly higher than that reported in other areas. Nevertheless, the trimodal distribution of TPMT activity varied depending on disease, and the proportion of patients with low activity values ranged from 0-0.8%. The drugs prescribed for the treatment of autoimmune diseases, including azathioprine/6-MP, modified TPMT activity, but the magnitude of this effect was very small and the differences found are probably irrelevant from the clinical point of view.

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Section: Discussionmentioning

confidence: 99%

Thiopurine Methyltransferase Activity in Spain: A Study of 14,545 Patients

et al. 2007

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“…It has been shown that differences in assay conditions can cause significant differences in TPMT activity measured in different laboratories [5]. We used a simple HPLC method to determine TPMP activity and produced results that seemed to be comparable to that of white populations (about 13 U ml -1 RBC) [3,4] and Korean children (12.4 U ml -1 RBC) measured by the standard radiochemical assay [23]. The 5.3-fold range in TPMT activity among Chinese Children in this study is similar to the 4.0-fold range observed in Korean Children [23].…”

Section: Discussionmentioning

confidence: 99%

“…We used a simple HPLC method to determine TPMP activity and produced results that seemed to be comparable to that of white populations (about 13 U ml -1 RBC) [3,4] and Korean children (12.4 U ml -1 RBC) measured by the standard radiochemical assay [23]. The 5.3-fold range in TPMT activity among Chinese Children in this study is similar to the 4.0-fold range observed in Korean Children [23]. In addition, this study observed minor and nonsignificantly higher TPMT activity in girls than boys.…”

Section: Discussionmentioning

confidence: 99%

Phenotyping and genotyping study of thiopurine S‐methyltransferase in healthy Chinese children: A comparison of Han and Yao ethnic groups

Zhang¹,

Guan²,

et al. 2004

Brit J Clinical Pharma

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AimsEthnicity 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. MethodsTPMT activity was measured in healthy Chinese children by a H PLC 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. ResultsThere 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. ConclusionThe 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.J.-P. Zhang et al. 16458 :2 Br J Clin Pharmacol

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“…A review of literature showed that Caucasians have higher median TPMT activity in erythrocytes than black populations [10,11,21], but North American Caucasians, European Caucasians, and Asian populations (healthy Korean children) [11,21,22] have approximately the same median TPMT activity in erythrocytes. The frequency of TPMT genetic variation in Thai children in the present study is the same as that reported in the Caucasian populations, therefore TPMT genotype in Thai children could reflect TPMT phenotypic activity in erythrocytes.…”

Section: Discussionmentioning

confidence: 99%