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Influence of TPMT polymorphisms on azathioprine-induced myelosuppression in Bangladeshi patients with systemic lupus erythematosus

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ARTICLE DOWNLOAD

Influence of TPMT polymorphisms on azathioprine-induced myelosuppression in Bangladeshi patients with systemic lupus erythematosus

10$

Mohammad Mamun Ur Rashid, Imtiaz Ahmed, Md. Asraful Islam, Tasnova Tasnim, Noor Ahmed Nahid, Mohd Nazmul Hasan Apu, Mir Md. Abdullah Al-Mamun, Md. Reazul Islam, Maizbha Uddin Ahmed, Masud Karim, Md. Nazrul Islam, Kazushige Yokota, Samia Shabnaz, Hasan Mahmud Reza, Mohammad Safiqul Islam & Abul Hasnat 

Abstract

Background

Thiopurine methyltransferase (TPMT) enzymes play a crucial role in azathioprine metabolism. Mutations in the enzyme initiate generation of excess thioguanine, which causes suppression of various cell lineages.

Objectives

The objectives of this study were to investigate the prevalence of TPMT mutation in Bangladeshi patients with systemic lupus erythematosus (SLE) requiring azathioprine therapy and its relation to the development of myelosuppression.

Methods

250 patients with SLE were enrolled, then monitored for myelosuppression adverse events for 4 months. TPMT*3C (rs1142345), TPMT*3B (rs1800460), and TPMT*2 (rs1800462) polymorphisms were analyzed using polymerase chain reaction–restriction fragment length polymorphism. The risk of myelosuppression (i.e., leukopenia, thrombocytopenia, and anemia) was estimated as the odds ratio (OR) with 95% confidence intervals (CIs) and p values.

Results

Of the 250 patients, 17 (6.8%) were heterozygous for the TPMT*3 mutation and 233 (93.2%) were homozygous for the wild type; no patients carried a homozygous mutation. Grade III/IV leukopenia, thrombocytopenia, and anemia occurred in 12.0%, 12.0%, and 27.9% of wild-type TPMT patients respectively; corresponding rates in heterozygous TPMT*3C patients were 70.6%, 64.7%, and 5.9%. Patients with Grade III/IV azathioprine-induced leukopenia were significantly more likely to have the heterozygous TPMT*3C genotype than the wild-type variant (OR 17.6; 95% CI 5.8–53.6; p < 0.0001), with comparable results for Grade III/IV azathioprine-induced thrombocytopenia (OR 13.4; 95% CI 4.6–39.2; p < 0.0001).

Conclusion

Patients with SLE carrying the TPMT*3C heterozygous genotype are at risk of azathioprine-induced myelosuppression.

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Year 2020
Language English
Format PDF
DOI 10.1007/s40267-020-00716-y