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

Abstract

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.

Guía de dermatitis atópica para México (GUIDAMEX): lineamientos usando metodología ADAPTE

“…Entre la población caucásica y afroamericana, el 10 y el 0.3% son heterocigotos y homocigotos, respectivamente, para este polimorfismo. Sin embargo en la población mexicana estos porcentajes se reportaron con una frecuencia considerablemente mayor en una serie de niños con leucemia: 27 y 0.8% respectivamente (Hospital Infantil de México, CDMX) 88 y en otra población de pacientes adultos con patologías autoinmunes: 10.1-12.4% 89 . El polimorfismo genético de TMPT con menos actividad enzimática puede conducir a mayor riesgo de mielotoxicidad, incluso fatal.…”