1. High frequency of mutant thiopurine S-methyltransferase genotypes in Mexican patients with systemic lupus erythematosus and rheumatoid arthritis
- Author
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Rosa Elda Barbosa-Cobos, Daniela Josabeth López-Cano, Julian Ramírez-Bello, Silvia Jiménez-Morales, and Mireya Ramirez-Florencio
- Subjects
Adult ,Male ,medicine.medical_specialty ,Genotype ,Purine analogue ,Polymorphism, Single Nucleotide ,Arthritis, Rheumatoid ,Young Adult ,03 medical and health sciences ,Thiopurine S-Methyltransferase ,0302 clinical medicine ,Gene Frequency ,Rheumatology ,Internal medicine ,medicine ,Humans ,Lupus Erythematosus, Systemic ,skin and connective tissue diseases ,Mexico ,Genotyping ,Alleles ,Genetic Association Studies ,030203 arthritis & rheumatology ,Autoimmune disease ,Thiopurine methyltransferase ,biology ,business.industry ,Methyltransferases ,General Medicine ,Middle Aged ,medicine.disease ,030220 oncology & carcinogenesis ,Rheumatoid arthritis ,Mutation ,Immunology ,biology.protein ,Female ,business ,Immunosuppressive Agents - 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.
- Published
- 2017