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High frequency of mutant thiopurine S-methyltransferase genotypes in Mexican patients with systemic lupus erythematosus and rheumatoid arthritis
- Source :
- Clinical Rheumatology. 37:963-970
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
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.
- 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
Subjects
Details
- ISSN :
- 14349949 and 07703198
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Clinical Rheumatology
- Accession number :
- edsair.doi.dedup.....6d8877d2ec56eb3f8f7d6c9f901a8d31