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

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 <italic>TPMT</italic> 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 <italic>TPMT</italic> 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 <italic>TPMT</italic>*2 (rs1800462), <italic>TPMT</italic>*3A (rs1800460 and rs1142345), <italic>TPMT</italic>*3B (rs1800460), and <italic>TPMT</italic>*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 (<italic>TPMT*2/*3A</italic>, 0.3%) and the <italic>TPMT</italic>*3B (0.5%) and <italic>TPMT</italic>*3C (1.0%) alleles were found in RA, but not SLE cases. Mexican SLE cases displayed the highest frequency of mutant <italic>TPMT</italic> genotypes worldwide. <italic>TPMT</italic> genotyping should be performed for Mexican patients with SLE and RA before prescribing purine analogs. [ABSTRACT FROM AUTHOR]