Clinical Rheumatology

, Volume 37, Issue 4, pp 963–970 | Cite as

High frequency of mutant thiopurine S-methyltransferase genotypes in Mexican patients with systemic lupus erythematosus and rheumatoid arthritis

  • Mireya Ramirez-Florencio
  • Silvia Jiménez-Morales
  • Rosa Elda Barbosa-Cobos
  • Daniela Josabeth López-Cano
  • Julian Ramírez-Bello
Original Article


Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are treated with immunosuppressive purine analogs, 6-mercaptopurine/6-thioguanine/azathiopurine, which are inactivated by thiopurine S-methyltransferase (TPMT). Non-synonymous polymorphisms in TPMT are associated with increased risk of adverse effects in patients treated with thiopurines. This study aimed to determine the frequency of the most common mutant TPMT alleles in Mexican patients with SLE (a prototype autoimmune disease) and RA (one of the most common autoimmune diseases in Mexico). Five hundred fifty-three consecutive patients from Central Mexico with SLE (178) and RA (375) were included. Subjects were genotyped to identify TPMT*2 (rs1800462), TPMT*3A (rs1800460 and rs1142345), TPMT*3B (rs1800460), and TPMT*3C (rs1142345) mutant alleles. DNA samples were assayed with the 5′ exonuclease technique and TaqMan probes. Mutant alleles were detected in 6.2 and 5.2% of SLE and RA cases, respectively. Of note, 12.4% of SLE cases and 10.1% of RA cases carried mutant genotypes. Among those, the null genotype (TPMT*2/*3A, 0.3%) and the TPMT*3B (0.5%) and TPMT*3C (1.0%) alleles were found in RA, but not SLE cases. Mexican SLE cases displayed the highest frequency of mutant TPMT genotypes worldwide. TPMT genotyping should be performed for Mexican patients with SLE and RA before prescribing purine analogs.


Mexican Mutant alleles Rheumatoid arthritis Systemic lupus erythematosus Thiopurine S-methyltransferase 


Funding information

This study was supported by the Consejo Nacional de Ciencia y Tecnología de México (CONACyT) (FOSISS; project no. 233107).

Compliance with ethical standards

Institutional ethics and research committees from the Juarez Hospital of Mexico approved this study, and written informed consent was obtained from each patient.




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Copyright information

© International League of Associations for Rheumatology (ILAR) 2017

Authors and Affiliations

  1. 1.Laboratorio de Genómica del CáncerInstituto Nacional de Medicina GenómicaMexico City, CDMXMexico
  2. 2.Servicio de ReumatologíaHospital Juárez de MéxicoMexico CityMexico
  3. 3.Unidad de Investigación en Enfermedades Endócrinas y MetabólicasHospital Juárez de MéxicoMexico City, D.F.Mexico

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