The association between thiopurine s-methyltransferase *3C polymorphism and azathioprine induced myelosuppression in Thai patients with systemic lupus erythematosus.

Abstract

Objective : To investigate the correlation between Thiopurine S-methyltransferase (TPMT) *3C polymorphism and azathioprine (AZA)-induced myelosuppression in Thai patients with systemic lupus erythematosus (SLE).

Methods : A total of 40 SLE patients taking AZA at King Chulalongkorn Memorial Hospital were included in this study. Blood samples from volunteers were collected in 3 ml EDTA tubes. TPMT*3C genotype was determined using PCR-RFLP assay and erythrocyte TPMT activity using HPLC method. Biochemical and clinical data were retrospectively evaluated after initiation of AZA therapy.

Results : Gene frequency of heterozygous TPMT*1/*3C was 10% (4/40) and *3C allele frequency was 5.0%. TPMT*1/*3C polymorphism was statistically significantly different (P = 0.005) and odd ratio of 45.0 folds (95%CI 3.092 – 654.900; p < 0.001), a higher risk for AZA-induced leucopenia than wild type. Furthermore polymorphism of TPMT*1/*3C gene was significantly associated with neutropenia (P = 0.027) and with an odd ratio of 31.0 folds (95%CI 1.896 – 506.771; p < 0.001). The enzyme activity in 18 patients was 39.29 ± 13.29 (SD) nmol 6-MTG/gHb/hr which was associated with TPMT genotype (p = 0.026).

Conclusion : TPMT genotyping and activity was significantly correlated with the risk of AZA-induced myelosuppressive in Thai SLE patients. The TPMT polymorphism may predict AZA-induced toxicity.