Ann Dermatol.  2017 Oct;29(5):529-535. 10.5021/ad.2017.29.5.529.

Thiopurine S-Methyltransferase Polymorphisms in Korean Dermatologic Patients

• Lee M
• Seo J
• Bang D
• Kim DY

• KMID: 2388902
• DOI: http://doi.org/10.5021/ad.2017.29.5.529

Abstract

BACKGROUND
Thiopurine S-methyltransferase (TPMT) is an important enzyme in the metabolism of thiopurines including azathioprine (AZA), 6-mercaptopurine, and 6-thioguanine. TPMT genotyping is widely used for screening of AZA-related toxicity during routine clinical practice in Korea. However, the data of TPMT genotypes and its AZA-related toxicity have not been studied in the field of dermatology.
OBJECTIVE
The aim of this study was to evaluate the genetic basis of TPMT polymorphism in Korean dermatologic patients and subsequently to investigate the relationship between mutant TPMT and adverse responses to AZA treatment.
METHODS
This study was retrospective, single-center study. One hundred forty-nine Korean dermatologic patients who underwent TPMT screening test were included. Each patient's medical records, the result of TPMT screening test, dose and treatment period of AZA, and side effects, were reviewed. Laboratory tests were assessed at each visit in order to monitor adverse drug reactions. Leukopenia grading was used in accordance with the common terminology criteria for adverse events (CTCAE) ver. 4.03.
RESULTS
Behçet's disease was the leading disorder among the patients. The frequency of TPMT mutation was 4.0% (6/149) among the participants in this study. Four of the six patients with genetic alterations were treated with a low-dose AZA regimen, but no AZA-related adverse events were observed.
CONCLUSION
Our results suggest that 1) TPMT polymorphisms in Korean dermatologic patients are similar to those previously reported in Asian patients with the most common mutant allele being TPMT*3C and 2) AZA can be used in the patients with these polymorphisms under a careful dosing regimen.

Keyword

Azathioprine; Behcet syndrome; Dermatology; Thiopurine S methyltranferase deficiency

MeSH Terms

6-Mercaptopurine
Alleles
Asian Continental Ancestry Group
Azathioprine
Behcet Syndrome
Dermatology
Drug-Related Side Effects and Adverse Reactions
Genotype
Humans
Korea
Leukopenia
Mass Screening
Medical Records
Metabolism
Retrospective Studies
Thioguanine
6-Mercaptopurine
Azathioprine
Thioguanine

Figure

• 

  Fig. 1 The time interval of bone marrow suppression after azathioprine (AZA) treatment. Total 40 patients with leukopenia were analyzed; grade 1 leukopenia (30), grade 2 leukopenia (8), and grade 4 leukopenia (2). Onset of leukopenia relates to time from the start of AZA treatment to the detection of leukopenia (medians are indicated).

• 

  Fig. 2 Changes in leukocyte counts over the follow-up interval in azathioprine (AZA)-treated patients heterozygous for a thiopurine S-methyltransferase (TPMT) mutation (n=4). The red dashed line indicates the threshold minimal value for grade 1 leukopenia according to the common terminology criteria for adverse events (CTCAE) ver. 4.03. The follow-up period ranged from 1 to 6 years. None of the AZA-treated patients developed leukopenia during the follow-up period. WBC: white blood cell.

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