Polymorphisms C677T and A1298C in the MTHFR gene in Mexican patients with rheumatoid arthritis treated with methotrexate: implication with elevation of transaminases.
Rheumatoid arthritis (RA) is the prototype of the rheumatic diseases worldwide. Methotrexate (MTX) is the drug of first choice in the treatment of this disease due to its immunosuppressant effect. However, side events are present in 30% of the patients. The C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are involved in the metabolism of MTX. Earlier studies reported an association between these polymorphisms and elevation of hepatic enzymes. We analyzed the frequencies of both polymorphisms and the presence of transaminasemia in 70 Mexican patients with rheumatic arthritis treated with MTX. The 19% (13/70) of patients had an increase in the serum level of transaminases. The A1298C polymorphism was associated with elevation of transaminases (P=0.024). The identification of MTHFR genotypes for C677T and A1298C polymorphisms could lead clinicians to identify patients in risk of elevation of transaminases, and give them an individualized treatment, as is a goal of pharmacogenetics.
Doctorado en Genética Humana, Instituto de Genética Humana, Centro Universitario Ciencias de la Salud (CUCS), Universidad de Guadalajara (U de G), Guadalajara, Mexico.
J P
JP
Mena
M
M
Salazar-Páramo
L
L
González-López
J I
JI
Gámez-Nava
L
L
Sandoval-Ramirez
J D
JD
Sánchez
L E
LE
Figuera
F J
FJ
Muñoz-Valle
M
M
Vazquez del Mercado
I P
IP
Dávalos
D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008727:Methotrexate / Q000009:adverse effects* / Q000493:pharmacokinetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008800:Mexico / Q000453:epidemiology; D016017:Odds Ratio; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D057285:Precision Medicine; D018570:Risk Assessment; D012307:Risk Factors; D000637:Transaminases / Q000097:blood*; D016896:Treatment Outcome; D015854:Up-Regulation
D018501:Antirheumatic Agents; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000637:Transaminases; D008727:Methotrexate