Thiopurine methyltransferase genotype and phenotype status in Japanese patients with systemic lupus erythematosus.

Abstract

We investigated the genotypic status of thiopurine methyltransferase (TPMT) polymorphism to evaluate the possible risk of the toxicity of azathioprine (AZA) in 68 patients with systemic lupus erythematosus (SLE). The allele frequency of TPMT mutation in the SLE group (2.9%) was higher than that in 174 Japanese healthy volunteers (1.1%), although it did not reach statistically significant difference (p=0.23). The mean value of TPMT activities in 51 subjects with TPMT*1/*1 was 40% higher than that of 4 subjects with TPMT*1/*3C in SLE group (18.1+/-6.1 nmol/h/ml packed red blood cells (pRBC) versus 13.2+/-3.2 nmol/h/ml pRBC; p=0.11). Two out of 4 SLE patients with TPMT*1/*3C had been treated with AZA, and one patient showed a leucopenia. The TPMT genotyping before AZA treatment is recommended for Japanese SLE patient group to avoid the AZA-induced adverse events, although detection of the patient with low TPMT activity by genotyping is still imperfect.

• Authors: Yuko Okada, Katsunori Nakamura, Tomoko Kodama, Kazue Ueki, Yoshito Tsukada, Akira Maezawa, Norifumi Tsukamoto, Yoshihisa Nojima, Takashi Ishizaki, Ryuya Horiuchi, Koujirou Yamamoto
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 28 Issue 11 Pg. 2117-9 (Nov 2005) ISSN: 0918-6158 [Print] Japan
• PMID: 16272700 (Publication Type: Journal Article)

Chemical References

• Immunosuppressive Agents
• DNA
• Methyltransferases
• thiopurine methyltransferase
• Azathioprine

Topics

• Adolescent
• Adult
• Aged
• Alleles
• Azathioprine (therapeutic use)
• DNA (genetics)
• Female
• Gene Frequency
• Genotype
• Heterozygote
• Humans
• Immunosuppressive Agents (therapeutic use)
• Japan (epidemiology)
• Lupus Erythematosus, Systemic (enzymology, epidemiology, genetics)
• Male
• Methyltransferases (blood, genetics, metabolism)
• Middle Aged
• Mutation (genetics)
• Phenotype
• Reverse Transcriptase Polymerase Chain Reaction