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

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.